HAI Book 2020 - Dec 18B

ding profiles of Flortaucipir, MK-6240
ssue samples across the spectrum of

Marquie1,2, Ana C Amaral1,2, Ramesh
M. Dooley1,2,5, Dominique Denbow1,2, Georges

din3,4, Teresa Gómez-Isla1,2

Hospital, Boston, MA, US
se, Charlestown, MA, US
ospital, Boston, MA, US
clear Medicine and Molecular Imaging,

husetts General Hospital, Boston, MA, US

ortaucipir, the most validated tau PET tracer thus far,
mer's (AD) but has relatively low affinity for tau
arget binding to neuromelanin- and melanin-
-generation tau tracers have recently been reported.
ve garnered most attention. Our recent data indicate
allels that exhibited by [18F]-flortaucipir.
6240 and [18F]-PI-2620 are critical for determining
easurement of progression of AD and other

properties and off-target profile of [18F]-flortaucipir,
ortem tissue specimens.

adiographic patterns of [18F]-flortaucipir, [18F]-MK-
ue material from AD and non-AD tauopathies (Pick’s
degeneration, chronic traumatic encephalopathy and
synucleinopathies, transactive response DNA-binding
TDP-43) and controls.

bind to tangles in AD but do not seem to bind to a
auopathies. [18F]-MK-6240 and [18F]-PI-2620 do not
clein or TDP-43. [18F]-MK-6240 and [18F]-PI-2620,
et binding to neuromelanin and melanin-containing
cross-blocking studies suggest that the three tracers

-target binding patterns of [18F]-MK-6240 and [18F]-
F]-flortaucipir. The correct identification of biological
ent for considering them as disease-specific and

]-AV-1451, [18F]-PI-2620, Autoradiography, PET.

01

Ikonomovic, Milos

Biochemical correlates of tau and amy
brains

Milos Ikonomovic1, Eric Abrahamson1, Julia Ko
Mathis1, Oscar Lopez1, William Klunk1

1University of Pittsburgh, Pittsburgh, PA, US

Objectives: Correlation analyses of tau-PET and amy
quantification of insoluble tau and Aβ concentrations.

Methods: [F-18]AV-1451 and [C-11]PiB PET scans
Alzheimer’s disease (AD; Cases #1,3,4; white males,
normal 91 y.o. white female (Case#2). Imaging-to aut
months (AV-1451 and PiB, respectively). Atrophy-co
concentrations of guanidine-HCl extracted total tau an
or formic acid extracted Aβ1-42 and Aβ1-40 in 17 fro
precuneus, and occipital cortex.

Results: AD neuropathology was intermediate in Cas
A3,B2,C2, respectively), and high in Case#3 and Case
hippocampal sclerosis, TDP-43, ARTAG, remote infa
Case#2 (Braak stage 4). [C-11]PiB PET and Aβ1-42 c
Case#2, weakly in Case#3, with a trend in Case#4. [C
[F-18]AV-1451 PET correlated with pSer396/total tau
correlation was observed in Case#3. [F-18]AV-1451 P
and trends for correlations were observed in Case#1 a
tau ratio correlated in Case#4.
Conclusions: Data confirm insoluble Aβ1-42 as the p
support the use of [F-18]AV-1451 for detection of neo
analyses of AV-1451 in additional cases with shorter
understand the relationship between the tracer’s PET r

Acknowledgment: We thank Avid Radiopharmaceutica
Keywords: tau, amyloid, PET, Alzheimer’s, neuropath

20

yloid PET imaging in four autopsy

ofler1, William Paljug1, Carl Becker1, Chester

yloid-β (Aβ)-PET with postmortem region-matched
.
were obtained from three subjects with probable
94, 91, and 62 y.o., respectively) and a cognitively
topsy time intervals were on average 23.5 and 34.5
orrected SUVR values were correlated with ELISA
nd tau phosphorylated at Ser396, Ser199, and Thr231
ozen gray matter samples from temporal, frontal,

se#1 and Case#2 (ABC scores A2,B3,C2 and
e#4 (both A3,B3,C3). Coexisting pathology included
arcts, and CAA. All cases were Braak stage 5 except
concentration correlated strongly in Case#1 and
C-11]PiB PET and Aβ1-40 correlated only in Case#1.
u ratio in Case#1 and Case#4, while a trend for
PET correlated with pSer199/total tau ratio in Case#4
and Case#3. [F-18]AV-1451 PET and pThr231/total

primary substrate for [C-11]PiB PET retention and
ocortical tau pathology in AD. Imaging-to-autopsy
imaging-to autopsy intervals are needed to better
retention levels and tau pathology burden.
als for providing [F-18]AV-1451 precursor.
hology

02

Schneider, Julie

KEYNOTE LECTURE 1

Title

Julie Schneider

Rush University, Chicago, IL, US

20

1

03

Thursday, January 16, 2020 - 10:45am - 11:30am

P2A: POSTER SESSION

Board Poster Title
#

100 Entorhinal tau pathology is associated with Adams | M
medial temporal lobe hyperactivity in aging Thomas |

80 Sex differences in the rates of cognitive decline Buckley |
associated with temporal lobe FTP-PET signal: Rentz | H
findings from the Harvard Aging Brain Study

Imaging synaptic and mitochondrial function in Clarke | M

73 frontotemporal dementia using [11C]UCB-J, Chen | Sc

[18F]BCPP-EF and [11C]SA4503 PET Rohrer

105 Longitudinal associations between lifestyle risk, Cody | Ko

β-amyloid, and cognition in late-midlife Chin | Cla

Cogswell

62 Correlation of QSM signal with Alzheimer’s Knopman
Disease biomarkers Kantarci

Schwarz

Collij | To

71 Quantitative regional amyloid burden and white Alves | Y

matter changes in preclinical AD Van Berc

AMYPAD

Individual variability in the cortical distribution

70 of elevated 18F-AV1451 and 11C-PIB in a Collins | E

heterogeneous sample of AD patients

Amyloid deposition disrupts functional Ingala | W
92 connectivity and graph properties within the Kate | Ko
de Goes |
default mode network Visser | d

93 Neuroinflammation in AD patients and Edison | L
correlates with amyloid and tau deposition

85 Sex differences in regional tau deposition in Edwards
cognitively impaired patients with Alzheimer’s Casaletto

disease

Higher microglia biomarker levels are

69 associated with slower rates of amyloid-beta Ewers | B
accumulation in humans and in a transgenic Sacher | B

mouse model of amyloid-beta

99 Early declines in learning and executive Farrell | P
function associated with accumulating Aβ not Properzi |

tau in low PIB adults

68 Association of tau tangle burden with Gatchel |
depressive symptoms in community dwelling Properzi |
older adults: a longitudinal study Chhatwal
Hanseeuw

78 Amyloid deposition affects the topography of Ye | Tour

cortical thinning in Lewy Body Disease | Johnson

107 Data-driven approach to characterization of tau Groh | Sv

accumulation in Braak staging groups Apostolo

A sensitive composite model to determine Hahn | Ki

77 subtle cognitive differences in preclinical
Alzheimer’s disease

Defining a Centiloid scale threshold predicting

61 long-term progression to dementia in patients Hanseeuw

attending the Memory Clinic: An F18- | Buckley

Flutemetamol amyloid-PET study

91 Prevalence of amyloid PET positivity in Kim | Jun
cognitively normal the East Asian populations

74 First-in-human evaluations of [11C]PS13 for Kim | Jua
imaging COX-1 and [11C]MC1 for imaging Morse | S
COX-2

20

N 2A

Authors Presenter Page

Maass | Berron | Harrison | Baker | Adams, Jenna 288
| Stanfill | Jagust 246

| Properzi | Schultz | Jacobs | Kirn | Buckley, Rachel 236
Hanseeuw | Johnson | Sperling

Mansur | Passchier | Lewis | Evans |
chwarz | Takano | Gunn | Cash | Rabiner | Clarke, Mica

oscik | Birdsill | Berman | Erickson | Cody, Karly 302
ark | Christian | Betthauser | Johnson 214
233
l | Wiste | Senjem | Therneau | Lowe | Cogswell, Petrice
n | Botha | Graff-Radford | Jones |
| Vemuri | Ferman | Boeve | Mielke |
| Gunter | Petersen | Jack

op | Stickney | Ingala | Tomassen | Lopes

Yaqub | Wink | Van 't Ent | Scheltens | Collij, Lyduine
ckel | Visser | Barkhof | Den Braber |

D consortium

Eckbo | McGinnis | Dickerson Collins, Jessica 232

Wink | Prent | van 't Ent | Tomassen | ten den Braber, 273
onijnenberg | Collij | Yaqub | Scheltens | Anouk 276
| Teunissen | Barkhof | van Berckel |
den Braber

Leng | Dani | Brooks Edison, Paul

| La Joie | Iaccarino | Kim | Baker | Edwards, Lauren 260
o | Miller | Jagust | Rabinovici

Brendel | Suarez-Calvet | Biechele | Ewers, Michael 229
Blume | Haass | Franzmeier

Papp | Buckley | Jacobs | Schultz | Farrell, Michelle 285
| Hanseeuw | Rentz | Johnson | Sperling
226
Marshall | Yang | Donovan | Buckley | Gatchel, Jennifer 244
| Quiroz | Rabin | Vannini | Amariglio | 308
l | Rentz | Blacker | Sperling | Johnson |
w

routoglou | Brickhouse | Katz | Growdon Gomperts,

n | Dickerson | Gomperts Stephen

valdi | Stage | Sanjay | Risacher | Saykin | Groh, Jenna
ova

im | Kim | Jang | Kim | Na | Chin | Seo Hahn, Alice 243

w | Malotaux | Dricot | Quenon | Cerman Hanseeuw, 211

y | Farrar | Ivanoiu | Lhommel Bernard

ng | Na | Kim | Won | Seo Kim, Jaeho 270
238
arez Anaya | Lee | Hong | Miller | Telu | Kim, Min-Jeong
Singh | Cortes-Salva | Henry | Ruiz-

04

Board Poster Title
#

Perdomo
Fujita | K

Evaluating the relationships among odor Klein | Ya
| Honig | B
64 identification, tau pathology and
neuroinflammation in Alzheimer’s disease

Distinct effects of APOE ε2 on Aβ in Lee | Lee
67 Alzheimer- and vascular-type cognitive Ossenkop
Kim | Kim
impairment Na | Seo

Longitudinal change in amyloid load over a 5-

79 year period in cognitively healthy APOE4 Luckett |

carriers versus non-carriers: Effect of reference Laere | D

region

Mild behavioral impairment is associated with Lussier | P

113 tau pathology in cognitively impaired elderly Benedet |

individuals Rosa-Net

Modeling the trajectory of tau deposition in Lussier | T

114 autosomal-dominant AD using the high-affinity Mathotaa

tau tracer [18F]MK6240 Rosa-Net

101 Clinicopathological confirmation of 123I-FP- Maltais |
CIT SPECT (ioflupane) quantification methods Przybelsk
in a spectrum of neurodegenerative syndromes Boeve | L
and associated pathologies

106 Exploring relationships between tau burden and Marterste

naming in the aphasic variant of AD Kim | Me

Elevated soluble phosphorylated tau is a marker Benzinge

65 of early amyloid PiB PET abnormalities and Benzinge

accumulation Bateman

112 A clinically-relevant scheme for qualitatively McGinnis
rating tau PET, amyloid PET, and MRI in Dickerson
neurodegenerative cognitive presentations

66 Cerebrospinal fluid and PET measures of tau Meyer | P
pathology may indicate different stages of AD Villeneuv
pathological progression

96 Use of the plasma amyloid-beta 42/40 ratio for Mielke | A
predicting amyloid PET in a community-based Syrjanen
population

111 Cerebrospinal fluid matrix metalloproteinases Moore | P
are associated with compromised white matter Landman
microstructure among older adults: the Hohman
Vanderbilt memory & aging project

94 Development of new alpha7 nicotinic receptor Nordberg
ASEM analogs for PET imaging Miranda A
Ågren | L

Associations between AD biomarkers and Oh | Corr
108 cognition among cognitively normal older

adults

[11C]MK-6884 PET tracer for M4 muscarinic Pascual |

75 cholinergic receptors in AD: Comparison with | Wang | L

[18F]FDG PET | Masdeu

Amyloid and tau PET burden are associated Pichet Bi
81 with white matter bundle abnormalities in Descoteau

asymptomatic individuals at risk of AD

104 Increased risk of AD in alcohol use disorder is Royse | H
not mediated by amyloid-beta in a middle-aged Narendra
cross-sectional cohort

Cross-sectional and longitudinal non-

86 dichotomized CSF/PET Aβ data support Sala | Nor
existence of “CSF+ first” vs. “PET+ first”

pathways of Aβ biomarkers changes

82 NeuroToolkit CSF biomarkers track the Salvadó |
progression of AD at very early stages and show Zetterberg
that inflammatory markers modulate cerebral Buckley |
amyloid accumulation

20

Authors Presenter Page

| Montero Santamaria | Liow | Zoghbi | 219
Katz | Pike | Innis 225

an | Johnson | Tomljanovic | Zou | Polly Klein, Julia
Brickman | Stern | Lee | Kreisl

e | Park | Choe | Park | Cheon | Hahn |

ppele | Kim | Kim | Yoo | Jang | Cho | Lee, Jin San
m | Jung | Park | DeCarli | Weiner | Yun |

Adamczuk | Schaeverbeke | Gabel | Van Luckett, Emma 245
Dupont | Vandenberghe 317
319
Pascoal | Therriault | Tissot | Savard | Lussier, Firoza 292
| Mathotaarachchi | Stevenson | Ismail | Lussier, Firoza 306
to | Gauthier 220

Therriault | Pascoal | Savard |
arachchi | Robb | Stevenson | Gauthier |
to

Jordan | Miyagawa | Lesnick | Maltais, Daniela
ki | Min | Dickson | Murray | Kantarci |
Lowe

eck | Sridhar | Coventry | Eldes | Wood | Martersteck,
esulam | Rogalski Adam

er | Benzinger | Joseph-Mathurin | McDade, Eric
er | Fagan | Xiong | Barthélemy |

s | Collins | Eckbo | Brickhouse | McGinnis, Scott 316
n

Pichet Binette | Gonneaud | Breitner | Meyer, Pierre- 222
ve Francois

Algeciras-Schimnich | Campbell | Mielke, Michelle 280
| Knopman | Jack Jr. | Peterson

Pechman | Acosta | Bell | Anderson | Moore, Elizabeth 315
n | Blennow | Zetterberg | Gifford | 277
| Jefferson

g | Lemoine | Mohan | Kuang | Nag | Jia |
Azpiazu | Datta | Arakawa | Varnäs | Nordberg, Agneta
Långström | Halldin

reia | Salloway Oh, Hwamee 311

Zanotti-Fregonara | Yu | Funk | Arbones 239
Li | Cheng | Anderson | Hostetler | Basile Pascual, Belen

inette | Theaud | Gonneaud | Poirier | Pichet Binette, 248
ux | Villeneuve Alexa 300

Himes | Minhas | Lopresti | Flanigan | Royse, Sarah
an

rdberg | Rodriguez-Vieitez Sala, Arianna 262

| Molinuevo | Milà-Alomà | Blennow |

g | Operto | Falcón | Batrla | Battle | Salvadó, Gemma 251

| Farrar | Minguillon | Fauria | Sánchez-

05

Board Poster Title
#

Benavide
study

Falcón | M

Calvet | P

T1rho MRI measurement of amyloid plaque Gomez | F

83 burden in cognitively unimpaired individuals: Gelpi | Sa

preliminary results in the ALFA+ cohort Baizán | S

Molinuev

ALFA stu

Gispert | L

84 Preliminary quantitative results of the Heeman |

AMYPAD prognostic and natural history study Vellas | S

Barkhof |

Effect of genetic risk, brain amyloid and

72 hippocampal volume on normal variation in Schaeverb
episodic memory performance in middle-aged Dupont |

and older adults

White matter disruption is an early and Scott | Sc

103 progressive feature of pre-symptomatic Dutch- Bateman

type hereditary cerebral amyloid angiopathy Martins |

Head-to-head comparison of F-Florbetaben and
88 F-Flutemetamol uptakes in the cortex, striatum Seo | Cho

and white matter

PI-2620 Tau PET is associated with amyloid- Stephens

90 beta levels in scans from subjects of the Scott | Ad

elenbecestat MissionAD program Krause | C

110 Using famous faces to investigate the neural Tennant |
systems involved in name retrieval

109 In vivo association of mitochondrial dysfunction Terada | T

with tau pathology in early AD Rosa-Net

Preliminary results: PiB and MK6240 regional Mayblyum

102 PET measures associated with digitized clock Jacobs | R

drawing performance Papp | Re

Associations between longitudinal cognitive Tudorasc

97 measures and cross-sectional tau in adults with Ellison | Z

Down syndrome Klunk | C

60 Longitudinal flortaucipir ([18F]AV-1451) PET Utianski |
uptake in Semantic Dementia Duffy | C
Knopman

76 Assessing Aβ, tau, and reactive astrocytosis in Villemag
aging and AD Mulligan
Rowe | O

63 Developing a novel alpha-synuclein (a-syn) Vokali | M
Jürgens |
positron emission tomography (PET) tracer for Gunn | Da
the diagnosis of Parkinson’s disease (PD) and Capotosti
Pfeifer | K
other a-synucleinopathies

Whitwell

95 Biological underpinnings of typical and atypical Weigand

Alzheimer’s dementia phenotypes Jones | Bo

| Josephs

89 Sleep impairment predicts longitudinal Winer | M
accumulation of β-amyloid

87 Personality and amyloid accumulation in Yoon | Ba
cognitively normal aging Jagust

Associations of amyloid deposition and FDG Zukotyns

98 uptake in aging and cognitively impaired elders Scott | Bo

with and without moderate to severe | Laforce

periventricular white matter hyperintensities Sossi | Th

20

Authors Presenter Page

es | Suárez-Calvet | Gispert | the ALFA

Montesinos | Grau-Rivera | Suárez- Salvadó, Gemma 254
Puig-Pijoan | Cascales | Navalpotro- Salvadó, Gemma 257
Fernández-Lebrero | Sánchez-Valle |
anfeliu | Rojas | Perissinotti | Niñerola-
Salvadó | Minguillon | Fauria |
vo | Sánchez-González | Gispert | the
udy

Lopes-Alves | Gray | Buckley | Collij |
| Salvadó | Scheltens | Frisoni | Ritchie |
Stephens | Ford | Molinuevo | Farrar |
| the AMYPAD Consortium

beke | Gabel | Adamczuk | Van Laere | Schaeverbeke, 235

Vandenberghe Jolien

chultz | Sohrabi | Gardener | Taddei | Scott, Matthew 296
| Benzinger | Johnson | Sperling |
Greenberg | Chhatwal | Investigators

o | Moon | Choe | Na Seo, Sang Won 264

| Bullich | Mueller | Berndt | De Santi |

damczuk | Suhy | Kaplow | Giroux | Stephens, Andrew 268

Chang | Albala

| Jagust | La Joie | Adams | Winer Tennant, Victoria 313

Therriault | Min Su | Savard | Ouchi | Terada, Tatsuhiro 312
to 293
281
m | Thibault | Moody | Farrell | Jiang | Thibault, Emma 207
Rubinstein | Sanchez | Katz | Sperling | 240
entz | Johnson
218
cu | Comer | Zammit | Laymon | Minhas |
278
Zaman | Ances | Johnson | Mathis | Tudorascu, Dana

Christian | Handen | Hartley | Cohen

| Whitwell | Martin | Botha | Schwarz | Utianski, Rene
Clark | Spychalla | Senjem | Petersen |
n | Jack, Jr. | Lowe | Josephs

gne | Harada | Doré | Furumoto | Villemagne,
n | Kudo | Krishnadas | Huang | Yanai | Victor
Okamura

Molette | Tsika | Ravache | Rodriguez | Vokali, Efthymia
Melo dos Santos | Sandiego | Russell |
armency | Piorkowska | Poli | Kroth |
i | Hliva | Sol | Marek | Stöhr | Lowe |
Kosco-Vilbois

l | Tosakulwong | Graff-Radford |

| Schwarz | Senjem | Ertekin-Taner | Whitwell, Jennifer
oeve | Knopman | Jack | Petersen | Lowe

Mander | Jagust | Walker Winer, Joseph 265
263
aker | Korman | Tennant | Harrison | Yoon, Bora
284
ski | Gaudet | Kuo | Adamo | Goubran |
octi | Borrie | Chertkow | Frayne | Hsiung Zukotynski,
| Noseworthy | Prato | Sahlas | Smith | Katherine
hiel | Soucy | Tardif | Black

06

Utianski, Rene

P60: Longitudinal flortaucipir ([18F]A
Dementia

Rene Utianski1, Jennifer Whitwell1, Peter Marti
Duffy1, Heather Clark1, Anthony Spychalla1, M
Knopman1, Cliff Jack, Jr.1, Val Lowe1, Keith Jo

1Mayo Clinic, Rochester, MN, US

Objective: To assess longitudinal volume loss and flo
dementia (SD).
Methods: Eight patients (3 female) with SD underwen
language assessments, FTP positron emission tomogra
(MRI) imaging at two visits, approximately one year a
white matter volume loss and FTP-PET uptake were p
age and sex-matched controls at both baseline and fol
cortical thickness and FTP uptake were also calculated
annualized change in clinical measures in the SD grou
Results: There was statistically significant worsening
between visits. At the voxel level, the SD patients sho
in the temporal lobes at first visit, which extended pos
hemisphere at follow-up. However, white matter loss
This extended posteriorly at follow-up, at which time
right hemisphere. Increased FTP uptake was noted in
lobe at first visit, which again extended posteriorly at
hemisphere at either visit.
Conclusions: The biological mechanisms of FTP sign
unknown. The findings suggest that while FTP uptake
robustly reflects the neurodegeneration underlying the

20

AV-1451) PET uptake in Semantic

in1, Hugo Botha1, Christopher Schwarz1, Joseph
Matthew Senjem1, Ronald Petersen1, David
osephs1

ortaucipir (FTP) uptake in patients with semantic

nt neurological, neuropsychological, speech, and
aphy (PET), and brain magnetic resonance imaging
apart. Voxel-level comparisons of MRI gray and
performed using SPM12, comparing SD patients to
llow-up visits. Individual annualized change in
d. Wilcoxon signed-rank tests were used to assess the
up.
g on tests of general cognition and lexical access
owed bilateral, left greater than right, gray volume loss
steriorly and more prominently in the right
was noted only in the left temporal lobe at first visit.
additional mild white matter loss was noted in the
the SD patients in the anterior portion of the temporal
follow-up, without any uptake in the right

nal in suspected underlying TDP-43 pathology are
e may track with disease progression, MRI more
e clinical presentation.

07

20

08

20

09

Keywords: semantic dementia; primary progressive a
21

aphasia; tau; PET; MRI
10

Hanseeuw, Bernard

P61: Defining a Centiloid scale thresh
to dementia in patients attending the M
Flutemetamol amyloid-PET study

Bernard Hanseeuw1,2, Vincent Malotaux1, Laure
Christopher Buckley4, Gill Farrar4, Adrian Ivano

1Clinique Universitaires Saint-Luc, Brussels, Belgium
2Massachusetts General Hospital, Boston, MA, US
3Charles University, Second Faculty of Medicine, Pra
4General Electrics Healthcare, Amersham, UK

Background: Regulatory authorities have approved v
adults with cognitive complaints to assess the presenc
Aβ-PET quantitative measures are associated with gre
recently, they lacked standardization. Therefore, the C
quantitation, was recently validated against autopsy da
visual and quantitative assessment in a clinical cohort
dementia after long follow-up as our standard of truth

Methods: Ninety-eight non-demented patients, aged 5
Luc University Hospital (Belgium) to participate in an
followed until dementia diagnosis or were clinically s
Flutemetamol images were visually assessed followin
as negative/positive by two independent experts. [18F]
Centiloid scale using GAAIN guidelines. We compute
baseline PET data and calculated negative (NPV) and
thresholds.

Results: Centiloid=26 provided the highest overall pr
Visual assessment as positive corresponded to Centilo
conflicting visual assessments (Fig.2). Centiloid=42 p
predictive value=86% (NPV=81%, PPV=91%). Centi
in PET-autopsy studies, provided lower PPV=74% (N
who were only followed for a median two years [0.8-3
but also decreased the PPV=67% (NPV=88%), reflect
dementia after short follow-ups (Fig.3).

Conclusions: Centiloid-threshold=26 best predicts pr
assessment provides similar predictive value (86%), w

21

hold predicting long-term progression
Memory Clinic: An F18-

ence Dricot1, Lisa Quenon1, Jiri Cerman3,
oiu1, Renaud Lhommel1

m

ague, Czech Republic

visual assessment of amyloid-PET images in older
ce of amyloid-β (Aβ) pathology. In research studies,
eater risk of progression to dementia; but until
Centiloid scale, providing standardized Aβ-PET
ata. We aimed to compare the predictive values of
t of non-demented patients, using progression to
h.

54-86, were recruited at the Memory Clinic of Saint-
n [18F]-Flutemetamol Aβ-PET study. Patients were
stable for a median six years [4.0-7.9]. [18F]-
ng the manufacturer recommendations and classified
]-Flutemetamol SUVr values were converted on the
ed ROC curves predicting subsequent dementia with
d positive (PPV) predictive values at various

redictive value=87% (NPV=85%, PPV=88%, Fig.1).
oid=42, excluding four cases (Centiloid=29-50) with
predicted subsequent dementia with an overall
iloid=12, suggested to detect incipient Aβ pathology
NPV=85%). Including twenty-five additional patients
3.9] did not modify the best threshold (Centiloid=26),
ting the many positive cases that did not progress to

rogression to dementia six years after PET. Visual
with higher specificity and lower sensitivity.

11

21

12

Keywords: Memory Clinic, Dementia prediction, Cen
21

ntiloid scale, visual assessment, Flutemetamol
13

Cogswell, Petrice

P62: Correlation of QSM signal with A

Petrice Cogswell1, Heather Wiste1, Matthew Sen
Knopman1, Hugo Botha1, Jonathan Graff-Radfo
Vemuri1, Tanis Ferman1, Bradley Boeve1, Mich
Gunter1, Ronald Petersen1, Clifford Jack1

1Mayo Clinic, Rochester, MN, MN, US

Objective: Altered iron metabolism has been hypothe
supported by work showing the presence of iron in be
cerebral iron load and established Alzheimer’s disease
susceptibility mapping (QSM) is a recently popularize
Our objective was to assess the relationship of cerebra
amyloid PET, tau PET, and neurodegeneration.
Methods: Individuals from the Mayo Clinic Study of
Center (ADRC) with multi-echo GRE imaging, amylo
included. Spearman correlations were performed betw
standardized uptake value (SUVR), tau PET SUVR, a
neurodegeneration).
Results: The study included 488 participants (280 ma
diagnoses of cognitively unimpaired 304(62%), mild c
syndrome 51(10%), Lewy body dementia 25(5%), fro
Spearman correlations (Figures 1, 2) were generally lo
meaningful pattern of correlation between QSM signa
Correlation between QSM signal and tau PET was gre
correlations elsewhere. The striatum also showed a po
Conclusions: Although iron has been found to be pres
of sufficient quantity for detection on QSM. Correlati
striatum is most likely due to the increase with age in
physiologic iron deposition in the basal ganglia, altho

21

Alzheimer’s Disease biomarkers

njem1, Terry Therneau1, Val Lowe1, David
ord1, David Jones1, Kejal Kantarci1, Prashanthi
helle Mielke1, Christopher Schwarz1, Jeffrey

esized to be associated with Alzheimer’s disease,
eta amyloid plaque. However, relationships between
e biomarkers remain unclear. Quantitative
ed technique used to infer tissue iron concentration.
al iron deposition based on QSM signal with age,

Aging (MCSA) and Alzheimer’s Disease Research
oid PET (PiB), and tau PET (flortaucipir) were
ween regional QSM signal and age, amyloid PET
and gray matter volumes (marker of

ale, median age 70 years, range 34-97 years) with
cognitive impairment 81(17%), Alzheimer’s clinical
ontotemporal dementia 11(2), and other 16(3%).
ow to moderate and demonstrated no clinically
al and amyloid PET or regional gray matter volume.
eatest in the striatum (Figure 3) without meaningful
ositive correlation between QSM signal and age.
sent in beta amyloid plaques, it does not appear to be
ion of QSM signal with tau PET SUVR and age in the
both off-target binding of the tau ligand and
ough other explanations are possible.

14

21

15

21

16

Keywords: Quantitative susceptibility mapping, amylo
21

oid PET, tau PET, Alzheimer’s disease
17

Vokali, Efthymia

P63: Developing a novel alpha-synucle
tomography (PET) tracer for the diag
other a-synucleinopathies

Efthymia Vokali1, Jerome Molette1, Elpida Tsik
Tanja Jürgens1, Antonio Melo dos Santos1, Chri
Gunn2, Vincent Darmency1, Kasia Piorkowska1
Capotosti1, Valérie Hliva1, Olivier Sol1, Kennet
Pfeifer1, Marie Kosco-Vilbois1

1AC Immune SA, Lausanne, Switzerland
2Invicro, A Konica-Minolta Company, Boston, MA, U
3Institute of Neurodegenerative Disorders, New Have

Objective: To develop an a-syn aggregate-selective P
including PD.

Methods: [18F]-ACI-Cpd-AE dynamic PET imaging w
idiopathic PD, 69.4±7.4 years and MDS-UPDRS ‘off’
49.7 years and MDS-UPDRS ‘off’ score 52) and five
[123I]DATscan screening in PD subjects showed abno
with HV. Specific retention of [18F]-ACI-Cpd-AE was
ratio (DVR) from kinetic analysis with an arterial inpu
(SUVr) from static analysis, using the middle frontal c
evaluated across the amygdala, brainstem, cerebellum
and white matter.

Results: [18F]-ACI-Cpd-AE displayed fast brain uptak
and high free fraction. In this small cohort, no signific
healthy controls and PD subjects was observed. Avera
was 1.16-1.23 in PD subjects and 1.15-1.3 in HV. Me
in left substantia nigra.

Conclusions: In house medicinal chemistry efforts led
PET tracer that preclinically binds selectively and wit
human (FiH) study, ACI-Cpd-AE demonstrated fast b
analyses of the FiH data (e.g., kinetic modeling, popu
expected higher levels of pathological brain a-syn agg
improved binding properties are being evaluated.

Keywords: alpha-synuclein, protein aggregation/misf

21

ein (a-syn) positron emission
gnosis of Parkinson’s disease (PD) and

ka1, Myriam Ravache1, Patrick Rodriguez1,
istine Sandiego2, David Russell2,3, Roger
1, Sonia Poli1, Heiko Kroth1, Francesca
th Marek3, Jan Stöhr1, David Lowe1, Andrea

US
en, CT, US

PET tracer for the diagnosis of synucleinopathies

was conducted over 90 min in five PD subjects (four
’ score 43.3±11.8, and one with a SNCA duplication,
healthy volunteers (HV, 58.4±18.8 years).
ormal striatal dopamine transporter uptake, compared
s evaluated by calculating the distribution volume
ut function and the standardized uptake value ratios
cortex as reference region. DVR and SUVr were
m, hippocampus, pallidum, substantia nigra, thalamus

ke, very low non-specific retention, rapid metabolism
cant evidence of cross-sectional difference between
aged across target regions the SUVr (30-90min) range
ean SUVr was 1.32±0.15 in PD and 1.19±0.18 in HV

d to the discovery of ACI-Cpd-AE, a potential a-syn
th high affinity to a-syn aggregates. In the first-in-
brain uptake and low non-specific retention. Further
ulation analysis) and evaluation in patients with
gregates are planned. In parallel, compounds with

folding, Biomarkers, PET Imaging

18

Klein, Julia

P64: Evaluating the relationships amo
and neuroinflammation in Alzheimer’

Julia Klein1,3, Jack Yan2, Aubrey Johnson1, Zelj
Lawrence Honig1, Adam Brickman1, Yaakov St

1Taub Institute, Columbia University Irving Medical C
2Mailman School of Public Health, Columbia Univers
3Weill Cornell Medical College, New York, NY, US

Background: Olfactory abilities are significantly imp
measured with the University of Pennsylvania Smell I
neuroinflammation, two pathological contributors to A
CSF biomarkers. UPSIT performance is inversely rela
PET. However, whether odor identification is related
pathology is unknown.

Methods: Participants were selected from an establish
had neuropsychological testing, brain MRI, and amylo
University of Pennsylvania Smell Identification Test (
three of these underwent 11C-PBR28 PET to measure
inflammation) and forty-one underwent 18F-MK-624
lumbar puncture to measure CSF concentrations of β -
tau (p-tau), and inflammatory biomarkers sTREM2 an

Results: Analysis of variance, controlling for age and
exhibit independent effects on UPSIT performance (p
performance and PET measures of neuroinflammation
middle/inferior temporal gyri, inferior parietal cortex
inverse relationships were seen for tau. UPSIT perform
of YKL-40, p-tau, and t-tau among amyloid-positive p

Conclusions: Amyloid-positivity and cognitive impai
identification, suggesting that 1) low UPSIT performa
individuals, and 2) impaired odor identification is asso
neurodegeneration. Odor identification ability appears
neuroinflammation in those on the Alzheimer’s contin

Keywords: MK6240, tau, neuroinflammation, odor id

21

ong odor identification, tau pathology
’s disease

jko Tomljanovic1, James Zou1, Krista Polly1,
tern1, Seonjoo Lee2, William C. Kreisl1

Center, New York, NY, US
sity Irving Medical Center, New York, NY, US

paired in Alzheimer’s disease (AD) and can be
Identification Test (UPSIT). Tau and
AD, can be measured in vivo using PET imaging and
ated to the amount of tau pathology measured with
to neuroinflammation or CSF measures of tau

hed research cohort of adults aged 50 and older who
oid PET. Fifty-four participants were administered the
(UPSIT) to measure odor identification ability. Fifty-
e the 18 kDa translocator protein (a biomarker of
40 PET to measure tau. Twenty-one participants had
-amyloid-42 (Aβ42), total tau (t-tau), phosphorylated
nd YKL-40.

d sex, showed that amyloid status and cognitive status
p < .01). Negative correlations between UPSIT
n were seen in medial temporal cortex, hippocampus,
and posterior cingulate cortex (p < .05). Similar
mance negatively correlated with CSF concentrations
participants (p < .05).

irment exhibit independent effects on odor
ance may signify risk of AD in cognitively normal
ociated with both AD- and non-AD-related
s to decline with increasing tau pathology and
nuum.

dentification, UPSIT

19

McDade, Eric

P65: Elevated soluble phosphorylated
PET abnormalities and accumulation

Tammie Benzinger1, Tammie Benzinger1, Nelly
Fagan1, Chengjie Xiong1, Nicolas Barthélemy1,

1Washington University School of Medicine, St. Louis

Background: Soluble phosphorylated tau (p-tau) is an
Alzheimer’s disease. Currently, p-tau is considered a m
recent work from the Dominantly inherited Alzheimer
hyperphosphorylation of tau occurring 5-10 years prio
to the timing of amyloid deposition.
Objective: To evaluate CSF p-tau as a method of clas
having abnormal levels of aggregated β-amyloid (PiB
accumulation.
Methods: A novel mass spectrometry based analysis
phosphorylated:unphosphorylated tau at multiple posi
mutation carriers (63% CDR 0) and was used to classi
their Receiver Operating Characteristic (ROC) curves
sectional, bivariate correlations between each p-tau iso
baseline p-tau measures to predict change in PiB-PET
Results: Phosphorylation of tau at position 217 had a
total tau 72% and pS202 69%, figure 1. We found a s
regional PiB-PET SUVR, with pT217 having the stron
However, only pT205 predicted longitudinal change i
not predict longitudinal change in PiB-PET.
Conclusion: Although abnormal levels of CSF p-tau i
demonstrate that soluble p-tau is much more strongly
plaques. These findings suggest important differences
tau could be an important measure of downstream resp

22

d tau is a marker of early amyloid PiB

y Joseph-Mathurin1, Tammie Benzinger1, Anne
Randall Bateman1

s, MO, US
n important biomarker of dysregulated tau in
measure of neurofibrillary tau pathology. However,
r Network study has demonstrated
or to identification of tau-PET changes, more similar

ssifying carriers of dominantly inherited mutations as
B-PET)) and a predictor of regional PiB-PET

of CSF p-tau quantified the ratio of
itions (pT181, pS202, pT205, pT217) from 183
ify participants as PiB-PET+ (SUVR >1.25) based on
s; in CDR 0 participants we further assessed the cross-
oform and cortical PiB-PET SUVR and the ability of
T SUVR using linear mixed-effects models.
97% AUC, followed by pT181 89%, pT205 74%,
similar order in the strength of correlations with
ngest correlations cross-sectionally, figure 2.
in PiB-PET in the inferior temporal while pT217 did

is considered a marker of NFT pathology we
linked to the initial development of amyloid beta
s between soluble/insoluble tau in AD and that CSF p-
ponse to amyloid specific therapies.

20

Keywords: phosphorylated tau, PiB PET, Tau PET, A
22

AUC
21

Meyer, Pierre-Francois

P66: Cerebrospinal fluid and PET me
different stages of AD pathological pro

Pierre-Francois Meyer1,2,3, Alexa Pichet Binette
Sylvia Villeneuve1,2,3,4

1Douglas Mental Health University Institute, Studies o
Centre, Montréal, QC, Canada
2Department of Psychiatry, McGill University, Montré
3McGill Centre for Integrative Neuroscience, McGill
4Department of Neurology and Neurosurgery, McGill
Background: Alzheimer’s disease-(AD) pathological
impairment. It was recently suggested that discrepanc
(Aβ) reflects timing of disease processes. We sought t
measures tau pathology.
Methods: Three-hundred and twenty-two participant
cognitive impairment and 11 with AD dementia) from
had available CSF and PET (flortaucipir) measures of
data-driven, clinically-relevant thresholds for CSF P-t
(SUVR≥1.37), we categorized tau abnormality as CSF
We compared these groups on demographic and clinic
binding in Braak stage-related ROIs. We also compar
accumulation and cognitive decline prior to flortaucip

22

easures of tau pathology may indicate
ogression

e1,2,3, Julie Gonneaud1,2, John Breitner1,2,3,

on Prevention of Alzheimer’s Disease (StoP-AD)
éal, QC, Canada
University, Montréal, QC, Canada
l University, Montréal, QC, Canada
l changes likely occur decades before cognitive
cy between CSF and PET measures of amyloid-beta
to assess whether similar observations were true for
ts (213 cognitively unimpaired, 98 with Mild
m the Alzheimer’s Disease Neuroimaging Initiative
f tau pathology within a 25-month interval. Using
tau (≥26.64 pg/mL) and a flortaucipir-PET meta-ROI
F-/PET-, CSF+/PET-, CSF-/PET+, and CSF+/PET+.
cal variables, Aβ-PET burden and flortaucipir-PET
red these groups’ five-year rates of CSF P-tau
pir-PET scanning.

22

Results: Among all participants, 210 were CSF-/PET
were CSF+/PET+ (Table 1, Figure 1). Tau-positive in
Aβ-PET burden. All CSF+/PET+ individuals were am
with MCI or AD (Figure 1). CSF+/PET- participants s
increased Flortaucipir-PET binding in early Braak RO
/PET- participants.

When compared with the CSF-/PET- group, CSF+/PE
CSF P-tau, had worse memory and executive function
in the five years preceding it (Figure 2).

22

T-, 63 were CSF+/PET-, 15 were CSF-/PET+ and 34
ndividuals by either measure showed an increase in
myloid-positive and 76% were clinically diagnosed
showed faster 5-year accrual of CSF P-tau and mildly
OIs (Figure 1), but similar memory decline than CSF-

ET+ individuals experienced faster 5-year accrual of
ning at flortaucipir-PET assessment and faster decline
23

Conclusions: Supra-threshold CSF P-tau without flo
AD-process without decline in cognitive functions and
CSF/PET tau measures coincide with stronger cogniti
indicator of progressing AD processes prior to substan
Keywords: Alzheimer’s disease, Biomarkers, Cerebro

22

ortaucipir abnormality may indicate an established
d widespread tau pathology. Concordance of
ive decline. CSF P-tau abnormality may serve as an
ntial cognitive impairment.
ospinal fluid, PET, tau

24

Lee, Jin San

P67: Distinct effects of APOE ε2 on Aβ
cognitive impairment

Jin San Lee1, Hyejoo Lee2, Seongbeom Park2, Y
Cheon2, Alice Hahn2, Rik Ossenkoppele3, Hee J
Jang2, Soo Hyun Cho4, Seung Joo Kim5, Jun Py
Charles DeCarli7, Michael Weiner8, Gyihyaon Y

1Kyung Hee University Hospital, Seoul, Korea
2Samsung Medical Center, Seoul, Korea
3VU University Medical Center, Amsterdam, Korea
4Chonnam National University Medical School, Gwan
5Gyeongsang National University Changwon Hospita
6Myungji Hospital, Goyang, Korea
7University of California, Davis, CA, US
8University of California, San Francisco, CA, US

Objective: To investigate the association between apo
burden measured with PET in patients with subcortica
with Alzheimer’s disease-related cognitive impairmen

Methods: A cross-sectional study was conducted in 3
evaluate the effects of APOE genotype or diagnostic g
logistic regression analyses. Further distinctive underl
by employing a latent class cluster analysis approach.

Results: In comparison with ε3 homozygotes, in the A
Aβ positivity (OR 0.43, 95% CI 0.23–0.79) while in t
5.01) showed a higher frequency of Aβ positivity. In p
Aβ positivity between the two groups (OR 5.12, 95%
ADCI group, the SVCI group had a significantly high
homozygotes. We also identified latent subgroups of A
Aβ-positive ADCI patients with APOE ε4 carriers.

Conclusions: Our findings suggest that APOE ε2 sho
SVCI and in those with ADCI. Our findings further su
positive SVCI patients with APOE ε2 carriers among

Keywords: Subcortical vascular cognitive impairment
E, Latent class analysis

22

β in Alzheimer- and vascular-type

Yeongsim Choe2, Yu Hyun Park2, Bo Kyoung
Jin Kim2, Seonwoo Kim2, Heejin Yoo2, Hyemin
yo Kim2, Young Hee Jung6, Key-Chung Park1,
Yun1, Duk L. Na2, Sang Won Seo2

ngju, Korea
al, Changwon, Korea

olipoprotein E (APOE) genotype and amyloid-β (Aβ)
al vascular cognitive impairment (SVCI) and in those
nt (ADCI).
310 patients with SVCI and in 999 with ADCI. To
group on Aβ positivity, we performed multivariate
lying features of the latent subgroups were examined
.
ADCI group, ε2 carriers showed a lower frequency of
the SVCI group, ε2 carriers (OR 2.26, 95% CI 1.02–
particular, there was an interaction of ε2 carriers for
CI 1.93–13.56), suggesting that in comparison to the
her frequency of Aβ positivity in ε2 carriers than in ε3
Aβ-positive SVCI patients with APOE ε2 carriers and

ows distinct effects on Aβ deposition in patients with
uggest that there is a distinctive subgroup of Aβ-
patients with cognitive impairments.
t, Alzheimer’s disease, Aβ positivity, Apolipoprotein

25

Gatchel, Jennifer

P68: Association of tau tangle burden
community dwelling older adults: a lo

Jennifer Gatchel1,2,4, Gad A. Marshall1,3,4, Hyun
Buckley1,3,7, Michael Properzi1,4, Yakeel T. Qui
Rebecca E. Amariglio1,3,4, Jasmeer Chhatwal1,3,4
Reisa A. Sperling1,3,4, Keith A. Johnson1,3,4, Ber

1Massachusetts General Hospital, Boston, MA, US
2McLean Hospital, Belmont, MA, US
3Brigham and Women’s Hospital, Boston, MA, US
4Harvard Medical School, Boston, MA, US
5Cliniques Universitaires Saint-Luc, Brussels, Belgium
6Harvard T.H.Chan School of Public Health, Boston,
7The Florey Institute, The University of Melbourne, V
8Hurvitz Brain Sciences Program, Sunnybrook Resear

Background: Depressive symptoms are thought to be
Alzheimer's disease (AD). However, the association b
preclinical AD remains poorly understood. In the curr
burden (amyloid and tau) on longitudinal change in de
adults.

Methods: 252 adults (age: 70.8 ±8.2; 61% females) fr
assessment with the 30-item Geriatric Depression Sca
were cognitively normal, without clinically significan
range: (0-16)). All underwent tau (18F-Flortaucipir) an
study year 3 or 4 to derive measures of inferior tempo
amyloid. A mixed model was employed with depende
random intercept and slope for each participant, and fi
cortical amyloid (at year closest to tau), time (time of
interaction of predictors with time.

Results: Baseline tau burden was associated with incr
EC tau, EC tau X time was a significant predictor of G
p=0.0002). Findings were similar for IT tau:(β=0.71; t
amyloid was not a significant predictor of longitudina
0.23, -0.08); p=0.11).

Conclusions: Baseline tau, but not amyloid, is indepe
symptoms over time. Future research incorporating lo
depressive symptoms is needed to delineate the tempo
increasing tauopathy in preclinical AD.

22