HAI Book 2020 - Dec 18B

76

Franzmeier, Nicolai

P130: Functional connectivity brain ar
accumulation in Alzheimer’s disease

Nicolai Franzmeier1, Julia Neitzel1, Anna Rubin
Ossenkoppele3,4, Oskar Hansson3,5, Michael Ew

1Institute for Stroke and Dementia Research, Klinikum
Universität LMU, Munich, Germany
2Department of Neurology, Skåne University Hospital
3Clinical Memory Research Unit, Department of Clini
4Alzheimer Center Amsterdam, Department of Neurol
Amsterdam, Amsterdam UMC, Amsterdam, The Nethe
5Memory Clinic, Skåne University Hospital, Lund, Sw

Background: In Alzheimer’s disease (AD), tau patho
evidence suggests that tau spreads in a connectivity-ba
patterns resemble functional brain networks in AD. H
connectivity (FC) predicts faster tau accumulation is u
samples whether fMRI-assessed FC predicts correlate
future tau-PET accumulation can be modeled by comb

Methods: We assessed baseline resting-state fMRI an
samples (ADNI/BioFiNDER: ~1.3/1.9yrs follow-up),
dementia patients (ADNI/BioFINDER: n=53/41) and
neocortical ROIs (Fig.1A), we estimated longitudinal
correlations of longitudinal tau-PET changes (Fig.1B)
matrix for each sample (Fig.1C). Additionally, we com
matrices. To test whether FC predicts correlated tau-P
between group-average FC and tau-PET covariance m
strongest tau-accumulation (i.e. “hotspots”) were pref
hotspots. Lastly, we determined whether a spreading m
future tau accumulation.

Results: Longitudinal temporo-parietal tau-PET incre
Ab+, higher inter-regional FC predicted stronger cova
b=0.38,p<0.001; BioFINDER: b=0.30,p<0.001,Fig.2A
networks (Fig.2C&D). In Ab+, FC of inferiotemporal
ROIs (ADNI: b=0.524,p<0.001; BioFINDER: b=0.39
combining baseline tau with FC predicted future tau a
BioFINDER: b=0.400,p<0.001,Fig.3C&D).

Conclusions: Connectivity predicts tau spread in AD,
Limiting tau-spreading may be a promising approach

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rchitecture predicts the rate of tau

nski1, Ruben Smith2,3, Olof Strandberg3, Rik
wers1

m der Universität München, Ludwig-Maximilians-

l, Lund, Sweden
ical Sciences Malmö, Lund University, Lund, Sweden
logy, Amsterdam Neuroscience, Vrije Universiteit
erlands
weden

ology is a key driver of cognitive decline. Preclinical
ased manner. Supporting this, cross-sectional tau-PET
However, whether inter-regional functional
unclear. Here, we assessed in two independent AD
ed longitudinal tau-PET accumulation and whether
bining baseline tau-PET with FC.

nd longitudinal AV1451 tau-PET in two independent
, including amyloid-positive (Ab+) preclinical to AD
Ab- controls (ADNI/BioFINDER: n=28/16). For 400
tau-PET changes. In Ab+, we computed ROI-to-ROI
), yielding a 400x400 covariance in tau-PET change
mputed fMRI-based group-average 400x400 FC
PET accumulation, we computed the association
matrices in Ab+. Next, we assessed whether ROIs with
ferentially connected to other tau-accumulating
model combining baseline FC and tau-PET predicted

ease was found in Ab+ but not in Ab- (p<0.005). In
ariance in tau-PET accumulation (ADNI:
A&B), which was consistent across functional brain
l tau-hotspots predicted tau accumulation in connected
98,p<0.001,Fig.3A&B). Our spreading model
accumulation in Ab+ (ADNI: b=0.471,p<0.001;

, supporting the view of transneuronal tau-spreading.
to slow AD progression.

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Keywords: Tau-PET imaging, Tau spreading, Alzheim
38

mer’s disease, functional connectivity
80

Groot, Colin

P131: How innocent is PART?: Mesia
worse cognitive performance in Aβ-ne

Colin Groot

1VU University Medical Center, Amsterdam UMC, Am
Background: It has been postulated that tau aggregat
aging process. Here we assess the effects of mesial tem
tau in Aβ-negative, cognitively normal individuals.
Methods: We assessed 47 cognitively normal subject
Biomarkers and Lifestyle (AIBL) cohort who underwe
MeTeR template was used to map regional tau and to
cortex, hippocampus, parahippocampus, and amygdal
assessed the effects of Me-tau (categorical [Me+/Me-]
composite memory, composite non-memory and the p
and on voxelwise tau-burden. Additionally, we assess
Results: Voxelwise analyses revealed that Me+ subje
and greater neocortical tau burden, which was corrobo
negatively associated with cognition and positively as
was marginally associated with higher age (p=0.08), b
Conclusion: Our findings show that, in Aβ-negative i
cognitive functioning, mesial temporal tau is associate
neocortical tau burden, indicating that tau in these sub
to cortical areas. While this tau-pathology is likely age
term “aging” implies.

38

al temporal tau is associated with
egative cognitively normal individuals

msterdam, The Netherlands
tion is present in many individuals and is part of the
mporal tau on cognitive performance and neocortical
ts with negative Aβ-PET from the Australian Imaging
went [18F]flortaucipir-PET imaging to assess tau. The
determine mesial temporal (Mecomprising entorhinal
la) tau-positivity (SUVR>1.2; n=10/47 [21.3%]). We
] and continuous) on cognition (i.e. MMSE,
pre-Alzheimer’s cognitive composite (AIBL version)
sed the effect of age and continuous Aβ-burden on tau.
ects had worse cognition compared to Me- subjects
orated by our observation that continuous Me-tau was
ssociated with neocortical tau. Furthermore, Me-tau
but there was no association with Aβ burden.
individuals performing within the normal range of
ed with worse cognitive performance and higher
bjects is starting to spread from mesial temporal areas
e-related (PART) it might not be as benign as the

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82

Keywords: PET, Flortaucipir, cognition, older adults,
38

, tau
83

Guo, Tengfei

P132: CSF P-tau detects cerebral tau a
amyloid positive elderly adults

Tengfei Guo1,2, William Jagust1,2, Susan Landau

1Helen Wills Neuroscience Institute, University of Cal
2Molecular Biophysics and Integrated Bioimaging, La
US

Objective: To investigate the relationship between CS
unimpaired (CU) and impaired elderly adults.

Methods: We analyzed amyloid PET, CSF P-tau and
participants. We examined the correlations between P
cortical ROIs and amygdala controlling for amyloid, d
because the strongest correlations were within the Tem
parahippocampal, fusiform, inferior-temporal, and mi
further analyses. P-tau and Temporal-metaROI FTP w
participants were classified as normal/abnormal on P-
23 and 1.27 respectively) and we compared baseline F
Alzheimer’s Cognitive Composite (PACC) and annua
examined prediction of annual FTP change using base
diagnosis, gender and age.
Results: Among Aβ+ participants, contemporaneous P
(45.1% PTAU+/FTP+; 25.5% PTAU-/FTP-); 24.2% w
5.2% were PTAU-/FTP+ (Fig.2). Compared to the PT
PTAU+/FTP- individuals had significantly higher FTP
and PTAU+/FTP+ groups both showed faster annual F
not contemporaneous FTP predicted subsequent temp
P-tau was predictive in Aβ+ participants and none of t

Conclusions: CSF P-tau is moderately associated wit
I-IV in Aβ+ individuals. Among Aβ+ individuals, abn
accumulation that occurs prior to abnormal FTP in me

38

accumulation earlier than tau PET in

u1,2

lifornia, Berkeley, Berkeley, CA, US
awrence Berkeley National Laboratory, Berkeley, CA,

SF P-tau and flortaucipir (FTP) PET in cognitively

FTP PET data from 356 CU, MCI and AD ADNI
P-tau and FTP SUVRs in 34 Freesurfer-defined
diagnosis, gender and age (Fig 1, FDR<0.05), and
mporal-metaROI (entorhinal, amygdala,
iddle-temporal) (Jack et al. 2017), it was selected for
were associated in Aβ+ participants only.153 Aβ+
-tau and Temporal-metaROI FTP (using thresholds of
FTP, hippocampal volume (HCV), Preclinical
al FTP change between these groups. Finally, we
eline amyloid, P-tau and FTP controlling for

P-tau and FTP were concordant for the majority
were PTAU+/FTP- (76% of which were CU), and
TAU-/FTP- group, PTAU+/FTP+ but not
P, lower HCV and PACC; whereas the PTAU+/FTP-
FTP increase (Fig.2C). Both amyloid and P-tau but
poral FTP increases in the whole cohort, whereas only
them was predictive in Aβ- participants (Fig.3).
th tau PET across ROIs predominately in Braak stages
normal CSF P-tau may reflect cerebral tau
edial and lateral temporal regions.

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86

Keywords: CSF P-tau, 18F-flortaucipir, tau PET, lon
38

ngitudinal, Alzheimer’s disease
87

Hanseeuw, Bernard

P133: Amyloid, tau, and atrophy in pr
longitudinal study

Bernard Hanseeuw1,2, Heidi Jacobs1, Aaron Sch
Michelle Farrell1, Matthew Scott1, Olivia Hamp
Johnson1

1Massachusetts General Hospital, Boston, MA, US
2Cliniques Universitaires Saint-Luc, Brussels, Belgium
Background: Amyloid-β (Aβ), tau, and atrophy are p
investigated their longitudinal associations in clinicall
Brain Study, testing the hypothesis that tau changes m
(HV).
Methods: Serial PiB-PET (Aβ, [1.9-8.5y]), Flortaucip
measures were obtained from 128 CN participants fol
a median of 3PiB-PET [2-5], 2 Flortaucipir-PET [2-4]
PVC-SUVr scaled on subcortical white matter. PiB w
in inferior temporal (IT) and entorhinal (EC) cortices.
v.6 and adjusted for intracranial volume. We predicted
slope in linear mixed-models and extracted PiB, tau, a
data were entered in age-adjusted correlation and med

Results: HV slope correlated with tau slope (Fig.1-2,
more strongly than with PiB slope (Fig.3, R2=0.05, p=
correlated with tau slope (R2>0.04, p<0.019), but not
increased the effect of IT-tau slope on HV slope (PiB-
effect of EC-tau slope on HV slope was not PiB-depen
that PiB slope and IT-tau slope successively mediated
baseline HV and age (Sobel-test=2.3, p=0.02). The m
because it was not associated with PiB, adjusting for b
Conclusions: In preclinical AD, longitudinal hippoca
entorhinal tau accumulation and an Aβ-dependent neo

38

reclinical Alzheimer’s disease: A

hultz1, Rachel Buckley1, Michael Properzi1,
pton1, Justin Sanchez1, Reisa Sperling1, Keith

m
pathological hallmarks of Alzheimer’s disease. We
ly normal (CN) participants from the Harvard Aging
mediate the effect of Aβ on hippocampal volume

pir-PET (tau, [0.8-6.0y]), and MRI (HV [1.3-7.0y])
llowed over a median of 5.1 years (y). Participants had
], and 3MRIs [2-5]. All PET data were expressed as
was measured in a neocortical aggregate, Flortaucipir
. Longitudinal HVs were processed using Freesurfer
d imaging data over time with random intercept and
and HV slopes for each subject. Baseline and slope
diation models to assess their associations.
IT: age-adjusted R2=0.12, EC: R2=0.15, p<0.0001)
=0.011). Adjusting for baseline data, HV slope
with PiB slope (R2=0.006, p=0.392). PiB levels
-by-Tau slope interaction: p=0.03). However, the
ndent (p=0.29). Sequential mediations demonstrated
d the effect of baseline PiB on final HV, adjusting for
mediation was not observed using EC-tau slope,
baseline data.
ampal atrophy is associated with an Aβ-independent
ocortical tau accumulation.

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89

Keywords: Longitudinal study; Tau-PET; Amyloid-PE
biomarkers

39

ET; Hippocampal Volume; temporal sequence of
90

Hansson, Oskar

P134: Increased levels and phosphory
earlier than changes in Tau PET in Al

Oskar Hansson1, Emelie Andersson1, Shorena Ja
Olof Strandberg1, Henrik Zetterberg2, Kaj Blenn
Stomrud1, Ruben Smith1, Sebastian Palmqvist1,

1Clinical Memory Research Unit, Lund University, Lu
2Department of Psychiatry and Neurochemistry, Instit
Academy at the University of Gothenburg, Gothenbur
3Eli Lilly and Company, Indianapolis, IN, US
The links between aggregation of β-amyloid (Aβ) and
unimpaired persons with Aβ plaques (abnormal Amyl
increased cerebrospinal fluid (CSF) total-tau (T-tau) a
which increased over time, despite lack of insoluble ta
increased prior to the threshold for Amyloid PET posi
Amyloid PET positivity. Further, Tau PET was only a
CSF P-tau. Effects of Amyloid PET on Tau PET were
high CSF tau predicted increased Tau PET rates. In 5x
started. These results show that Aβ pathology may ind
phosphorylation (measured in CSF), which is followe
several years later in humans.
Keywords: CSF, PET, tau pathology, early diagnosis

39

ylation of soluble tau proteins occur
lzheimer’s disease

anelidze1, Rik Ossenkoppele1, Philip Insel1,
now2, Xiyun Chai3, Jeffrey Dage3, Erik
Niklas Mattsson1

und, Sweden
tute of Neuroscience and Physiology, the Sahlgrenska
rg, Sweden
d tau in Alzheimer’s disease are unclear. Cognitively
loid positron emission tomography, PET) had
and phosphorylated tau (P-tau181 and P-tau217),
au aggregates (normal Tau PET). CSF T-tau and P-tau
itivity, while Tau PET started to increase after
abnormal in Aβ+ individuals with already increased
e mediated by CSF P-tau (and partly by T-tau), and
xFAD mice, CSF tau increased when Ab aggregation
duce changes in soluble tau secretion and
ed by tau aggregation (measured with Tau PET)

91

Harada, Ryuichi

P135: Preclinical characterization of [
tracer with little off-target binding

Ryuichi Harada1,2, Pradith Lerdsirisuk3, Du Yiq
Takahiro Morito1, Hiroyuki Arai2, Kazuhiko Ya
Nobuyuki Okamura2,3,5

1Department of Pharmacology, Tohoku University Gr
2Department of Geriatrics and Gerontology, Division
and Cancer, Tohoku University, Sendai, Japan
3Cyclotron and Radioisotope Center, Tohoku Univers
4Department of Neurology, Tohoku University Gradua
5Division of Pharmacology, Faculty of Medicine, Toh
Japan

Background: Recent validation studies have revealed
to detect tau aggregates, bound to monoamine oxidase
develop highly selective tau tracers identified a novel
this study was to evaluate the binding property of [18F
aggregates in vivo.

Methods: [18F]fluoroethyl harmine and [3H]THK-535
recombinant MAO-A and MAO-B, respectively. In vi
performed using [18F]THK-5562, [18F]SMBT-1 (a nov
[18F]PI-2620, [3H]MK-6240, and [18F]florbetaben. Ph
assessed in normal mice after intravenous injection of

Results: THK-5562 was highly selective to tau aggreg
synuclein, TDP-43, MAO-A and MAO-B. In vitro aut
intense laminar binding of [18F]THK-5562 to the neoc
to the basal ganglia of AD and PSP. [18F]THK-5351 a
ganglia of PSP, which was not matched with tau imm
initial brain uptake and rapid washout after intravenou
[18F]THK-5562 did not penetrate the blood-brain barr

Conclusions: [18F]THK-5562 is a promising candidat
enable accurate monitoring of tau aggregates in the hu

Keywords: radiopharmaceticals, tau, autoradiograph

39

[18F]THK-5562, a novel tau PET

qing1, Michinori Ezura4, Yuki Shimizu3,
anai1, Yukitsuka Kudo2, Shozo Furumoto3,

raduate School of Medicine, Sendai, Japan
n of Brain Science, Institute of Development, Aging
sity, Sendai, Japan
ate School of Medicine, Sendai, Japan
hoku Medical and Pharmaceutical University, Sendai,

d that [18F]THK-5351, which was originally designed
e B (MAO-B) with high affinity. Further efforts to
tau PET tracer named [18F]THK-5562. The aim of
F]THK-5562 as a PET tracer for imaging tau

51 were used for competitive binding assay to
itro autoradiography of the human brain sections was
vel MAO-B tracer), [18F]THK-5351, [18F]AV-1451,
harmacokinetics and metabolism were additionally
f [18F]THK-5562.
gates over other proteins including amyloid-β, α-
toradiography of the human brain demonstrated the
cortex of AD, in contrast with no significant binding
and [18F]AV-1451 showed the binding to the basal
munohistochemistry. [18F]THK-5562 showed high
us administration and the radiolabeled metabolites of
rier in mice.
te for selective tau PET tracer in AD, which will
uman brain.
hy

92

Hsiao, Ing-Tsung

P136: Comparison of tau PET imagin
THK5351 in Alzheimer’s disease patie

Ing-Tsung Hsiao1,2, Kun-Ju Lin1,2, Chin-Chang

1Dept MIRS and Healthy Aging Center, Chang Gung
2Dept Nuclear Medicine, Chang Gung Memorial Hosp
3Dept Neurology, Chang Gung Memorial Hospital, Ta

Aim: To compare the brain uptake pattern of the tau t
Alzheimer’s diseases (AD) patients and normal contro
Methods: A total of 5 NC subjects and 10 AD patient

39

ng using 18F-APN-1607 and 18F-
ents and normal controls

Huang3, Kuo-Lun Huang3

University, Taoyuan, Taiwan
pital, Taoyuan, Taiwan
aoyuan, Taiwan

tracers 18F-APN-1607 and 18F-THK-5351 in
ols (NC)
ts underwent both 18F-APN-1607and 18F-THK-5351
93

PET scans. MRI was performed to enable image regis
50-60min post-injection for 18F-APN-1607 and 18F-TH
normalized to MNI space. Frontal, temporal, parietal a
Braak-like VOIs for stages 1/2, 3/4 and 5/6 were delin
SUVRs for VOIs were computed using inferior cerebe
Results: For the mean images of both tracers (Figure
thalamus was observed, as expected in NC for 18F-TH
for 18F-APN-1607. The same pattern was observed in
SUVr was seen across different regions in NC for 18F-
across different regions for 18F-THK-5351. For AD, 1
basal ganglia, and relatively more dynamic SUVr rang
stage 3/4 and 5/6 VOIs.
Conclusion: In this preliminary study of two tau trace
notably, no off-target uptake was seen for 18F-APN-16
ganglia and thalamus. Regional quantitation indicates
NC for 18F-APN-1607 than for 18F-THK-5351. Future
identification of an optimal reference region for 18F-A
Keywords: Tau PET imaging, 18F-APN-1607, 18F-TH

39

stration. PET images were acquired 90-110min and
HK-5351, respectively. Each image was spatially
and occipital lobe volumes of interest (VOIs) and
neated from corresponding individual MRI scans.
ellar cortex as reference region for both tracers.
1), higher background uptake in basal ganglia and
HK-5351, while no background signal was seen in NC
n the SUVr plots (Figure 2), and almost the same
-APN-1607, while the regional SUVr level varied
18F-APN-1607 displayed no off-target binding in
ges than 18F-THK-5351, particularly in the Braak
ers, different distribution patterns were observed, and
607 as compared to 18F-THK-5351 in the basal
s better differential diagnostic power between AD and
e work will include longitudinal study and
APN-1607 imaging.
HK5351, Alzheimer’s disease

94

Iaccarino, Leonardo

P137: In vivo amyloid-PET and tau-P
Alzheimer’s Disease: taking the LEAD

Leonardo Iaccarino1, Renaud La Joie1, Orit Lesm
Karine Provost1, Jessica A. Collins2, Paul S. Ais
Fagan6, Tatiana M. Foroud7, Constantine Gatson
Andrew J. Saykin7, Arthur W. Toga11, Prashanti
Radford13, Lawrence S. Honig14, David T. Jones
Chiadi U. Onyike17, Emily J. Rogalski18, Stephe
Wingo21, Robert Koeppe10, Brad C. Dickerson22
Gil D. Rabinovici1

1Memory and Aging Center, Department of Neurology
California, San Francisco, CA, USA, San Francisco, C
2Massachusetts General Hospital, Boston, MA, USA,
3Alzheimer’s Therapeutic Research Institute, San Dieg
4Mayo Clinic, Rochester, MN, USA, Rochester, MN, U
5Brown University, Providence, RI, USA, Providence,
6Department of Neurology, Washington University Sc
US
7Indiana University, Indianapolis, IN, US
8Department of Biostatistics, Brown University, Provi
9University of California, San Francisco, San Francis
10University of Michigan, Ann Arbor, MI, USA, Ann A
11Laboratory of Neuro Imaging, Stevens Neuroimagin
University of Southern California, Los Angeles, CA, U
12Washington University School of Medicine, St. Loui
13Mayo Clinic, Jacksonville, FL, USA, Jacksonville, F
14Columbia University Medical Center, New York, NY
15Houston Methodist Neurological Institute, Houston,
16David Geffen School of Medicine at University of Ca
Angeles, CA, US
17Johns Hopkins University, Baltimore, MD, USA, Ba
18Northwestern University, Chicago, IL, US
19Butler Hospital, Providence, RI, USA, Providence, R
20University of Pennsylvania, Philadelphia, PA, USA,
21Emory University School of Medicine, Atlanta, GA,
22Massachusetts General Hospital/Harvard Medical S
23Alzheimer’s Association, Chicago, IL, US
24Department of Radiology and Imaging Sciences, Ind
IN, US

Background: Patients with sporadic early-Onset Alzh
less likely to harbor age-related co-pathologies and th
amyloid and tau pathology in AD. We here present pr
Early-Onset Alzheimer’s Disease Study (LEADS). Th
2018 and October 2019.

Methods: Ninety-eight patients (aged 59±4 years, see
Mild Cognitive Impairment due to AD were included
amyloid-PET (FBB-PET) was used to assign patients

39

PET evidence in early-onset
DS

man-Segev1, David Soleimani-Meigooni1,
sen3, Bret J. Borowski4, Ani Eloyan5, Anne M.
nis8, Clifford R. Jack Jr.4, Joel H. Kramer9,
i Vemuri4, Gregory S. Day12, Neill R. Graff-
s4, Joseph C. Masdeu15, Mario Mendez16,
en Salloway19, David A. Wolk20, Thomas S.
2, Liana G. Apostolova24, Maria C. Carrillo23,

y, Weill Institute for Neurosciences, University of
CA, US
Boston, MA, US
go, CA, USA, San Diego, CA, US
US
, RI, US
chool of Medicine, St. Louis, MO, USA, St. Louis, MO,

idence, RI, USA, Providence, RI, US
sco, CA, USA, San Francisco, CA, US
Arbor, MI, US
ng and Informatics Institute, Keck School of Medicine,
USA, Los Angeles, CA, US
is, MO, USA, St. Louis, MO, US
FL, US
Y, USA, New York, NY, US
, TX, USA, Houston, TX, US
alifornia, Los Angeles, Los Angeles, CA, USA, Los

altimore, MD, US

RI, US
, Philadelphia, PA, US
USA, Atlanta, GA, US
School, Boston, MA, USA, Boston, MA, US

diana University School of Medicine, Indianapolis,

heimer’s Disease (EOAD) (aged 65 or younger) are
hus provide a framework to study the interplay of
reliminary results from the ongoing Longitudinal
his report is based on data collected between August

e Tab.1) meeting clinical criteria for probable AD or
from 12 US centers. At screening, 18F-Florbetaben
to EOAD (amyloid-positive) or EOnonAD (amyloid-

95

negative) subgroups based on visual rating and semi-q
Flortaucipir tau-PET (FTP-PET) available. FBB-PET
analysis in meta/Braak regions were performed using
eight cognitively-normal controls (aged 55±6 years) w
Results: Out of the 98 patients, 77 were amyloid-posi
(EOnonAD). Compared to EOAD, EOnonAD patients
male (Tab.1). EOAD patients showed elevated FTP-P
regions of interest (Fig.1). EOAD showed elevated FT
occipital regions (Fig.2). Some EOAD cases showed m
suggestive of AD focal subtypes, including posterior-d
with EOnonAD did not differ from controls in any PE
EOnonAD patients showed abnormal FTP-PET patter
conditions, e.g. asymmetric mild temporoparietal bind
Conclusions: Preliminary LEADS findings show very
of early-onset AD patients. Our evidence suggests tha
needed given the relatively high rate of negative FBB

39

quantification. Eighty-six participants had 18F-
neocortical composite and FTP-PET regional
structural 3T-MRI acquired concurrently. Thirty-
were included.
itive (EOAD) and 21 were amyloid-negative
s had higher MMSE scores and were more frequently
PET SUVR compared to EOnonAD and controls in all
TP-PET binding in temporoparietal, frontal and
mild temporoparietal FTP-PET binding or patterns
dominant and asymmetric patterns (Fig. 2). Patients
ET-based amyloid- or tau-PET measurement. Few
rns, possibly suggestive of other neurodegenerative
ding (Fig. 2).
y elevated FTP-PET binding in a multicentric cohort
at amyloid screening in young symptomatic patients is
B-PET scans.

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97

Keywords: Early-Onset AD, tau-PET, amyloid-PET, L
39

LEADS
98

Iaccarino, Leonardo

P138: Multimodal in vivo investigation
associations with cerebrospinal fluid N

Leonardo Iaccarino1, Renaud La Joie1, Lauren E
Julie Pham1, Kiran Chaudhary1, Laura Fenton2,
Baker4, Bruce Miller1, William Jagust2,4, Anne F

1Memory and Aging Center, Department of Neurology
California, San Francisco, San Francisco, CA, US
2Helen Wills Neuroscience Institute, University of Cal
3Knight Alzheimer Disease Research Center, Departm
MO, US
4Lawrence Berkeley National Laboratory, Berkeley, C
5Department of Radiology and Biomedical Imaging; U
Francisco, CA, US

Background: CSF Neurofilament Light (NfL) chain a
inflammatory processes, respectively, and have been p
Alzheimer’s Disease (AD) course. Their relationship w
elucidated.

Methods: Fifty-one amyloid-positive patients (aged 6
4.2±2.3) with a clinical diagnosis of AD dementia or M
Imaging markers included PET with18F-Flortaucipir (F
(neurodegeneration/hypometabolism), whereas fluid-b
markers of Aβ1-42, total-tau (T-tau), phosphorylated-ta
covarying for age and sex were tested between all flui
repeated in subgroups split by median age (60 years).

Results: CSF NfL and YKL40 correlated significantly
r=.52, p<0.001, respectively, Figure 1). NfL, not YKL
p<0.001 and r=0.39, p=0.09). Neither marker correlat
Aβ1-42 (r=0.03, p=1 and r=-0.07, p=1) (see Figure 2). R
in age subgroups, with a stronger effect observed in y
in older patients). YKL40 and T-tau levels, conversely
p=0.007) but not younger (r=0.23, p=1) patients. NfL
anterior temporal, and insular 18F-FTP binding, partia
correlated with CSF T-tau (Figure 3). YKL40 levels c
in older patients, although at lower statistical threshol
CSF-to-18F-FDG correlations.

Conclusions: Our findings suggest that the degree of
(NfL) associate more with tau rather than amyloid pat

39

n of amyloid and tau biomarkers
NfL and YKL40 levels

Edwards1, Orit Lesman-Segev1, Amelia Strom1,
Gina Jerome3, Mustafa Janabi4, Suzanne
Fagan3, Gil Rabinovici1,2,4,5

y, Weill Institute for Neurosciences, University of

lifornia, Berkeley, Berkeley, CA, US
ment of Neurology, Washington University, St. Louis,

CA, US
University of California, San Francisco, San

and YKL40 proteins reflect axonal injury and
proposed to be novel candidate biomarkers for
with AD amyloid and tau markers has yet to be fully

61±7 years, N=29/51 females, MMSE 22±6, CDR-sb
Mild Cognitive Impairment due to AD were included.
FTP), 11C-PiB (PIB), and 18F-FDG
based markers included cerebrospinal fluid (CSF)
au181 (P-tau), NfL and YKL40 proteins. Correlations
id and imaging biomarkers. All analyses were

y with age (partial Spearman rho=.35, p=0.01 and
L40, correlated significantly with T-tau (r=0.6,
ted with P-tau (r=0.24, p=1 and r=0.26, p=0.82) or
Relationships between NfL and T-tau were confirmed
younger patients (r=0.72, p=0.007 vs. r=0.58, p=0.03
y, were significantly associated in older (r=0.64,

levels correlated significantly with medial frontal,
ally overlapping with regions in which FTP-PET
correlated with left temporoparietal 18F-FTP binding
lds (p<0.01 uncorrected). There were no significant

neuroinflammation (YKL40) and neurodegeneration
thology.

99

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