HAI Book 2020 - Dec 18B

ET processing on uptake variability

rd Joules1, Robin Wolz1

on Tomography (PET) based on [18F]-AV-1451 (Tau-
nical trials but the role of registration on Tau-PET

image registration tools for Tau-PET pre-processing.
ontrols, 29 mild cognitively impaired, 33 AD) were
g Tau-PET ([18F]-Flortaucipir) and T1w-MRI data
from ADNI-core.
AP and rigidly registered into native Tau-PET space,

he cerebellum grey matter as reference region, were
Braak-like composites.
wo registration pipelines were highly correlated among
th ADNI-reported measures (respectively

correlated with the group-variable (Spearman’s r=-

TK) was bound to the inter-quartile range -2.26 to
solute relative terms) with left-skewed distribution
over high-SUVR values.
es accurate registration to anatomical-MRI for

erent registration schemes to be possibly under the
rocessing schemes that may have a significant impact
gn.
iffered between registrations with Cohen’s d=-0.167;-
reference).
would require (5% significance, 80% power, paired-
and ANTS-registrations.

26

Rabiner, Eugenii

P40: MIND MAPS: Assessment of the
reticulum - synaptic axis in neurodege
[11C]SA4503 and [11C]UCB-J PET im

Eugenii Rabiner1,2, Ayla Mansur1,3, Ashwin Ven
Gennaro Pagano2, Mica Clarke5, Yvonne Lewis
Brooks7, Lefkos Middleton3, Marios Politis2, Jo
C. Evans9, Laurent Martarello9, Laigao Chen10,
Tsukada13, Jan Passchier1, Roger N. Gunn1,3, M

1Invicro, London, UK
2King’s College London, London, UK
3Imperial College London, London, UK
4UKDRI @ Imperial College London, London, UK
5University College London, London, UK
6University of Cambridge, Cambridge, UK
7University of Newcastle, Newcastle, UK
8AbbVie, Deerfield, MA, US
9Biogen, Cambridge, MA, US
10Pfizer, Cambridge, MA, US
11Takeda, Cambridge, MA, US
12Celgene, Summit, NJ, US
13Hamamatsu Photonics, Hamamatsu, Japan

Background: A common feature of neurodegenerativ
reticulum (ER) function, contributing to the loss of sy
investigation of the mitochondria/ER/synaptic axis ma
biomarker common to all neurodegenerative disease. M
receptor (S1R) and the synaptic vesicular glycoprotein
these processes. We used [18F]BCPP-EF, [11C]SA45
comprehensive MRI battery to determine MC1, S1R a
volunteers (HV, n=31), patients with Alzheimer’s dise
fronto-temporal dementia (FTD, n=5) in the context o

Methods: Dynamic PET tissue, blood and metabolite
90 minutes for each subject (Fig 1). Analysis with an
regional parameters (DVR-1, for [18F]BCPP-EF and
differences were assessed using One-Way ANOVA fo
assess the relationship between imaging parameters an

Results: Significant effect of age on MC1 and SV2A
MMSE correlated significantly with MC1 density in t
Patients had significantly lower MC1 and SV2A dens
driven primarily by reductions in AD and FTD patien
correlated significantly with the patient’s MMSE scor

Conclusions: We have demonstrated significant reduc
markers, that correlate with global cognitive scores, in
the notion of a widespread mitochondrial and synaptic
disease.

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e mitochondrial - endoplasmic
eneration by [18F]BCPP-EF,
maging

nkataraman3,4, Geraint Price3, Heather Wilson2,
s1, Paul M. Matthews3,4, James B. Rowe6, David
onathan D. Rohrer5, Robert Comley8, Karleyton
Adam J. Schwarz11, Karl Schmidt12, Hideo
MIND MAPS Consortium1

ve disease is a failure of mitochondrial/endoplasmic
ynapses and ultimately neurons. Multimodal
ay enable the development of a mechanistic
Mitochondrial complex 1 (MC1), the sigma-1
n 2A (SV2A) are attractive molecular markers for
503 and [11C]UCB-J PET in conjunction with a
and SV2A status respectively, in the brains of healthy
ease (AD, n=12), Parkinson’s disease (PD, n=12) and
of the MIND-MAPS programme.

e data for the three radioligands, were acquired over
appropriate kinetic model, enabled the estimation of
[11C]UCB-J, VT/fp for [11C]SA4503). Group
or the individual regions. Kendall’s tau was used to
nd subjects age and MMSE scores.

density were seen across multiple regions in HV.
the Thalamus, Cingulate and Caudate (Fig 2).
sity across multiple brain regions (10-36%, Fig 3),
nts. SV2A and MC1 density in the patient group
re (Fig 2).

ctions in mitochondrial and synaptic molecular
n patients with neurodegeneration. Our results support
c dysfunction in patients with neurodegenerative

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Keywords: SV2A, Mitochondrial Complex 1, Sigma 1
13

receptor, Neurodegeneration, PET
30

Rahmouni, Nesrine

P41: Associations between Neurogran
Alzheimer’s disease

Nesrine Rahmouni1,2, Andrea Benedet1,2, Ashto
Pascoal1,2, Hlin Kvartsberg8, Mira Chamoun1,2,
Therriault1,2, Jenna Stevenson1,2, Melissa Savard
Thomas1,2, Serge Gauthier1,3, Henrik Zetterberg

1McGill University Research Center for Studies in Ag
2Translational Neuroimaging Laboratory-McGill Uni
3Douglas Hospital Research Center, Montreal, QC, C
4Department of Psychiatry and Neurochemistry, Instit
Academy at the University of Gothenburg, Mölndal, S
5Wallenberg Centre for Molecular and Translational
Sweden
6King’s College London, Institute of Psychiatry, Psych
Neuroscience Institute, London, UK
7NIHR Biomedical Research Centre for Mental Health
London & Maudsley NHS Foundation, London, UK
8Clinical Neurochemistry Laboratory, Sahlgrenska Un
9Department of Neurodegenerative Disease, UCL Inst
10UK Dementia Research Institute at UCL, London, U

Introduction: Neurogranin, a postsynaptic protein, ha
depletion and is known to be detected at elevated leve
Alzheimer’s disease (AD). There is currently no publi
neurogranin levels in CSF and imaging biomarkers of

Objective: To investigate whether neurogranin in CS
and tau across the AD spectrum.

Methods: The present study was conducted in a popu
unimpaired individuals, 57 cognitively unimpaired, 25
neurogranin was quantified using an in-house ELISA
[18F]AZD4694 PET and accumulation of tau was asse
[18F]MK6240 standardized uptake value ratio (SUVR
110 min post-injection, respectively, using cerebellum
regression model evaluated the relationship between t
[18F]AZD4694 and [18F]MK6240.

Results: In the present study, positive correlations we
both accumulation of tau and amyloid deposition inde
association was present were the temporal, occipital a
corrections for multiple comparisons.

Conclusion: The associations between neurogranin an
converge to brain regions vulnerable to synaptic deple
is a biomarker for neurodegeneration in the spectrum

13

nin and imaging biomarkers of

on Nicholas4,5,6,7, Cécile Tissot1,2, Tharick A.
Min Su Kang1,2, Firoza Lussier1,2, Joseph
d1,2, Sulantha Mathotaarachchi1,2, Emilie

g4,8,9,10, Kaj Blennow4,8, Pedro Rosa-Neto1,2

ging, Montreal, QC, Canada
iversity, Montreal, QC, Canada
Canada
tute of Neuroscience & Physiology, the Sahlgrenska
Sweden
Medicine, University of Gothenburg, Gothenburg,

hology & Neuroscience, Maurice Wohl Clinical

h & Biomedical Research Unit for Dementia at South

niversity Hospital, Mölndal, Sweden
titute of Neurology, Queen Square, London, UK
UK

as recently been proposed as a biomarker of synaptic
els in cerebrospinal fluid (CSF) at early stages of
ished study showing a correlation between
f AD in vivo.

SF is correlated with brain accumulation of amyloid-β

ulation of 111 individuals (17 young cognitively
5 mild cognitively impaired and 12 AD). CSF
assay. Amyloid deposition was assessed with
essed with [18F]MK6240 PET. [18F]AZD4694 and
Rs) were calculated between 40 to 70 min and 90 to
m grey matter as the reference region. A voxel-based
the accumulation of neurogranin and the PET markers

ere found between levels of neurogranin in CSF and
exed by PET-imaging. The brain regions where this
and parietal areas. These regions survived to

nd the hallmarks of AD pathophysiological process
etion. These results support the claim that neurogranin
of clinical presentations of AD.

31

Keywords: neurogranin, synaptic depletion, in vivo bi
13

iomarkers, cerebrospinal fluid
32

Riphagen, Joost

P42: Linking APOE ε4, blood-brain b
to Alzheimer’s pathology

Joost Riphagen1,5, Inez Ramakers1, Whitney Fre
Marcel Verbeek3, Frans Verhey1, Heidi Jacobs1,

1Department of Psychiatry & Neuropsychology, Maas
Neuroscience, Alzheimer Center Limburg, Maastricht
2Division of Nuclear Medicine and Molecular Imagin
Hospital, Harvard Medical School, Boston, MA, US
3Department of Neurology, Donders Institute for Brai
Laboratory Medicine, Translational Metabolic Labor
Nijmegen, The Netherlands
4Department of Neurology, Cliniques Universitaires S
Catholique de Louvain, Brussels, Belgium
5Department of Radiology, Athinoula A. Martinos Cen
Hospital, Harvard Medical School, Charlestown, MA
Abstract
The APOE-ε4 genotype is a risk factor for late-onset A
pathology. Given the increased risk of blood-brain-ba
carriers, we aimed to examine whether blood-brain-ba
relationship between APOE and Alzheimer’s disease k
fluid (CSF). We applied bootstrapped regression (figu
albumin CSF/plasma ratio (a BBB/BSCFB function m
inflammation markers) and CSF p-Tau181 and Amylo
participants (age 38-83 years) from a university memo
Our results showed that relationship between BBB dy
and these associations appear be driven by the APOE-
vascular factors are also part of the pathway to AD pa
response, and could become targets for trials focused

13

barrier dysfunction and inflammation

eeze1, Linda Pagen1, Bernard Hanseeuw2,4,

,2,5

stricht University, School for Mental Health &
t, the Netherlands., Maastricht, The Netherlands
ng, Department of Radiology, Massachusetts General
in, Cognition and Behaviour, Department of
ratory, Radboud University Medical Center,
Saint-Luc and Institute of Neurosciences, Université
nter for Biomedical Imaging, Massachusetts General
A, US

Alzheimer’s disease (AD) as well as vascular
arrier dysfunction and inflammation among APOE-ε4
arrier dysfunction and inflammation contribute to the
key pathologies, as measured in the cerebrospinal
ure 2) and path analyses ( figure 1) involving Q-
marker), interleukins (IL-1β, IL6 and IL-12p70;
oid− β 1−42 (AD pathology markers) of 97
ory clinic.
ysfunction and AD pathology is modulated by IL-6
-ε4 genotype. This suggests that APOE-ε4 related
athology, in synergy with an elevated immune
on delaying AD.

33

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Keywords: APOE-e4, Amyloid, ptau, blood-brain bar
13

rrier, Inflammation
35

Rubinstein, Zoe

P43: Heterogeneity of tau PET signal

Zoe B Rubinstein1, Heidi IL Jacobs1, Jean Augu
Danielle Mayblyum1, Emma Thibault1, Justin S
Teresa Gomez-Isla1, Cristina Lois-Gomez1, Juli

1Massachusetts General Hospital, Boston, MA, US
2Cliniques Universitaires, Saint-Luc, Brussels, Belgiu
3Brigham and Women Hospital, Boston, MA, US
Background: Neuropathology studies have shown he
amygdala, finding higher levels in the accessory basal
sought to determine whether a similar pattern was det
Methods: Fifty-six adults (47 cognitively normal, 9 M
acquisition on the GE Discovery MI PET/CT, and MM
1). We identified amygdala sub-nuclei with FreeSurfe
and sampled in 3 ROI, comparable to PET camera res
(BasAcc), Lateral, and an aggregate of smaller nuclei
related ROI MK6240 SUVR (reference, cerebellar gra
SUVR in whole amygdala, hippocampus, entorhinal c
Results: In a sub-sample of people with the greatest M
cognitively normal, 7 MCI-AD) the majority exhibited
portion of the amygdala (Figure 1C). In the full sampl
(r=-0.10, p=0.458), CMCA (r=-0.05, p=0.706), or Lat
between neocortical PiB and amygdalar substructure t
hippocampus, entorhinal cortex, and inferior temporal
r>0.8, p<0.001).
Conclusion: As AD tauopathy progresses to involve t
distributed. Instead, specific substructures are selectiv
basal nuclei. Considering the connectivity patterns of
tauopathy, the heterogeneity of tau accumulation in th
phenotypes.

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in the sub-nuclei of the amygdala

ustinack1, Michael Properzi1, J Alex Becker1,
Sanchez1, Aaron Schultz1, Bernard Hanseeuw1,2,
ie Price1, Reisa Sperling1,3, Keith A Johnson1,3

um

eterogeneity of tau deposition across sub-nuclei of the
l nuclei and lower levels in the lateral nuclei. We
tectable in vivo with tau PET.
MCI-AD) received a 3T MRI, PiB and MK6240 PET
MSE, GDS, and digital clock drawing test (see Table
er 6.0 (Saygin and Kliemann et al. 2017, see Fig. 1),
solution: an aggregate Basal and Accessory basal
including Central, Medial and Cortical (CMCA). We
ay) to age, amyloid burden (PIB FLR), and MK6240
cortex, and inferior temporal gyrus.
MK6240 binding in the amygdala (N=14, 7
d high signal (MK6240 SUVR > 1.5) in the medial
le, we found no correlation between age and BasAcc
teral (r=-0.04, p=0.781). There was a relationship
tau (all r>0.6, p<0.001). Tau in the whole amygdala,
l also correlated with tau in the substructures (all

the amygdala, deposition is not uniformly
vely involved, particularly the basal and accessory
these substructures and their association with
he amygdala could relate to different cognitive

36

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Keywords: amygdala, MK6240, FreeSurfer, PiB
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39

Scott, David

P44: MCI patients demonstrate reliab
uptake across three exams

David Scott1, Katarzyna Adamczuk1, Beth Gorm

1Bioclinica, Newark, CA, US
2Bioclinica, Philadelphia, PA, US
Background: 18F-AV1451 PET allows in vivo visua
contributes to a neurodegenerative cascade toward Al
uptake patterns complicate the assessment of longitud
PET signal as a clinical trial endpoint. From a biomar
reliably worsening (increasing) uptake presents the op
could show some effect. We investigated whether reli
patients with serial 18F-AV1451 PET exams.
Methods: We identified individuals with at least three
(http://adni.loni.ucla.edu), yielding 120 analyzable ex
patients (average between first and last exams 794 day
summed, co-registered into MRI space, normalized in
resolution. Whole-brain SUVR maps were generated w
Regional SUVR was extracted for AAL2 ROIs, and S
analysis. ROIs and voxels were classified as reliably i
2 and visits 2 and 3.
Results and Conclusions: MCI patients demonstrated
brain regions than normal subjects. MCI patients show
ROIs (t = 2.4, two-tailed p < 0.02), with the most prom
parahippocampal gyri in addition to posterior cingulat
functionally-defined ROI in right parahippocampal gy
increasing (t = 3.6, two-tailed p = 0.001). These result
untreated, 18F-AV1451 uptake can be expected to con
Keywords: tau, PET, AV1451, MCI, longitudinal

14

bly increasing 18F-AV1451 PET

man2, Maureen Runkle2, Joyce Suhy1

alization of tau pathology, the accumulation of which
lzheimer’s Disease. Interindividual differences in
dinal trajectories, posing a challenge in utilizing tau
rker perspective, a spatiotemporal distribution yielding
ptimal trajectory against which a putative therapy
iably increasing signal could be detected in MCI

e 18F-AV1451 PET exams in the ADNI database
xams over 21 normal subjects, 17 MCI and 2 AD
ys ± 122). Raw PET data was motion-corrected,
nto MNI template space, and smoothed to uniform
with an inferior cerebellar cortex reference region.
SUVR maps were entered into SPM voxelwise
increasing when uptake increased between visits 1 and

d reliably increasing uptake in significantly more
wed reliably increasing tau signal in the majority of
minent effects seen in fusiform, lingual,
te, amygdala and inferior temporal lobe. A
yrus yielded the most dramatic evidence of reliable
ts suggest a distributed spatial pattern where, left
ntinually accumulate over time.

40

Seibyl, John

P45: Development of a qualitative rea
presence and extent of brain tau depos
imaging

John Seibyl1, Cristian Salinas2, Raj Rajagovinda
Laurent Martarello2

1Institute for Neurodegenerative Disorders, New Have
2Biogen, Cambridge, MA, US

Introduction: In vivo characterization of pathologic d
imaging is a promising tool in drug development trials
tauopathies. [18F]MK-6240 is a radiotracer with high
neurofibrillary tangles that shows favorable off-target
of the present investigation was to develop a visual as
(abnormal yes/no) for tau positivity, and further, to ch
use in longitudinal assessments.

Methods: Data from 218 subjects who underwent [18
generate 60-90 min average static images for each par
medicine physician blind to participants’ diagnosis to
this review, a visual read method was developed for fi

Results: A three step read process was developed: 1)
brain regions, 3) summary assessment. For Step 2, eig
assessed as showing “no abnormal uptake”, “<25% in
involvement” of the region. Step 3 entails application
“normal”, “abnormal AD”, or “abnormal not AD”. Us
diagnosis had a sensitivity of 81% and specificity of 9

Conclusion: In this ongoing study using [18F]MK-62
both binary determination of the presence of abnorma
These cross-sectional results suggest the feasibility of
progressive tau changes in AD. Further validation in l
Keywords: tau, positron emission tomography , Alzhe

14

ad method for characterizing the
sition using [18F]MK-6240 PET

an2, R. Matthew Hutchison2, John Beaver2,

en, CT, US

deposition of tau protein in human brain by PET
s of Alzheimer’s Disease and other
h selectivity and subnanomolar affinity for
t binding, brain penetration, and kinetics. The purpose
ssessment method that provides a binary outcome
haracterize changes in regional cortical tau uptake for

8F]MK-6240 scans at 9 different sites was used to
rticipant. These were reviewed by an expert nuclear
identify common patterns of brain uptake. Based on
ield testing, adjustment, re-testing, and finalization.
scan quality assessment, 2) interrogation of specified
ght bilateral hippocampal and cortical regions are
nvolvement”, “25-75% involvement”, or “>75%
of three rules to render a characterization of
sing this method, an independent read blinded to
94% relative to the clinical diagnosis.
240 PET,a read algorithm was developed permitting
al brain tau and also the extent of cortical involvement.
f a Braak-like visual PET characterization of
longitudinal cohorts is pending
eimer’s disease, imaging biomarker

41

Solingapuram sai, Kiran kumar

P46: PET imaging of [11C]MPC-6827
murine models of Alzheimer's disease

Kiran Kumar Solingapuram Sai1, Shannon Mac
Suzanne Craft1

1Wake Forest School of Medicine, Winston Salem, NC
2Columbia University Medical Center, New York, NY,
Introduction: In healthy neurons, tau binds to microt
disease (AD) brain, tau is detached from MTs and pho
for early AD biomarkers that capture changes in neuro
Aβ and tau pathology. MT PET imaging agent could b
molecular imaging tools, providing a solid platform to
recently reported the radiochemical synthesis of the fi
6827 and it’s in vivoPET imaging in normal mice. In t
[11C]MPC-6827 in amyloid β (Aβ)-over expressing (
transgenic and wild-type AD mice.
Methods: Dynamic PET imaging was performed in b
APP-PS1 at 3m, 18m and 22 months; 5xFAD (at 15 m
120 ± 20 μCi of [11C]MPC-6827. Ex vivo post-PET b
WT APP/PS1 and 5xFAD mice (n=3/group).
Conclusions: [11C]MPC-6827 showed significant low
5xFAD and P301S mice over their corresponding wild
in brain corroborated well with the microPET/CT ana
Next steps: We will correlate [11C]MPC-6827 uptake
in NHP model of AD at our ADRC.
Therefore, [11C]MPC-6827 could serve as a potentia
diseases (ADRD).
Keywords: PET, Microtubule, novel biomarker, AD m

14

7, a microtoubule-based PET tracer in

cauley1, Christopher Whitlow1, Akiva Mintz2,

C, US
, US
tubules (MTs) to regulate its stability. In Alzheimer’s
osphorylated at multiple sites. There is a critical need
onal integrity and stability, especially in the context of
be an ideal bridge between classical biomarkers and
o image brain functions (early on) in AD. We have
irst brain-penetrating MT PET ligand, [11C]MPC-
this presentation, we report the in vivo evaluations of
(APP-PS1, 5xFAD) and tau-over expressing (P301S)

both transgenic (TG) and wild-type (WT) (n=4/group);
months) and P301S mice (at 8 months) by injecting
biodistribution studies were performed in both TG and

wer radioactive uptake in the transgenic APP-PS1,
d-type control mice. Post-PET biodistribution results
alysis.
e with tau pathologies and perform PET/CT imaging

al early PET imaging biomarker of AD related

mice model, imaging

42

Soucy, Jean-Paul

P47: Quantifying the relationship betw
and local atrophy to inter-regional con
data

Jean-Paul Soucy1,2, Fatameh Mohammadi2, Ped
Savard1, Min Su Peter Kang1, Joseph Therriault

1McGill University, Montreal, QC, Canada
2PERFORM Centre - Concordia University, Montreal
Models of tau distribution in AD brains assume that p
connecting specific regions. While this is a logical hyp
demonstrating that connectivity between two regions
thickness across regions. We assessed this on human d
We have included in this study 35 AD subjects from A
different times, Ta and Tb, and a T1 weighted MRI. E
(NP: no significant change between time 1 and 2 in hi
progressors (P: significant change between time 1 and
considered to represent how far advanced the patients
matched controls to assess normal regional cortical th
images were segmented in 68 standard regions, for wh
extracted. No DTI-MRI being available, we used a sta
Project). We used Moran’s I statistics, which allow fo
(here, connectivity) on the correlation between values
highly connected brain ROIs also show higher correla
connected ones.
The p-values of Moran’s I indices for NPs and Ps in b
<0,01. Hence, we conclude that there is a strong impa
parameters across the whole brain. This confirms that
as predicted by connectivity across regions.
Keywords: Tau, Atrophy, Progression, Model

14

ween the brain distributions of tau
nnectivity based on individual human

dro Rosa-Neto1, Tharick Pascoal1, Melissa
t1, Habib Benali2

l, QC, Canada
progression proceeds through propagation along axons
pothesis, it has never been formally tested by
results in correlation of tau SUVRs or cortical
data from subjects of the ADNI cohort with AD.
ADNI with 2 PET Tau studies (18F-florbetapir) at 2
Eighteen subjects turned out to be non-progressors
ippocampal SUVRs values) while 17 subjects were
d 2 in hippocampal SUVRs values). This criterion was
s were in their disease. We also evaluated 19 age-
hickness. Using FreeSurfer, the pre-processed T1
hich SUVRs and cortical thickness values were
andard connectivity map (Human Connectome
or determination of the impact of “spatial proximity”
s of a parameter in different regions, to assess whether
ation of SUVRs/thickness than more weakly

both SUVRs and thickness at Ta and T2 were all
act of structural connectivity on the correlation of both
t indeed, in vivo, tau aggregates do diffuse in the brain

43

Stevenson, Jenna

P48: Monitoring disease pathophysiol
acquisitions: The McGill TRIAD Coho

Jenna Stevenson1,2, Mira Chamoun1,2, Tharick A
Kang1,2, Sulantha Mathotaarachchi1,2, Joseph Th
Cecile Tissot1,2, Firoza Lussier1,2, Tasha Vinet-C
Gagné1,2, Meong Joung1,2, Sarah Sbeiti1,2, Moni
Pedro Rosa-Neto1,2

1McGill University, Verdun, QC, Canada
2Translational Neuroimaging Laboratory, Montreal, Q
3Douglas Hospital Research Centre, Verdun, QC, Can

Introduction: The Translational Biomarkers in Aging
the biomarker trajectories and interactions between pa
part of the McGill Research Centre for Studies in Agi
preclinical dementia diagnosis. TRIAD’s main objecti
amyloid-b and tau and their role in the progression of
role of neuroinflammation, epigenetics and synaptic d

Study Design: Inclusion into the TRIAD cohort begin
participant’s eligibility. Participants sign an ethically a
biofluids (blood, urine, saliva and cerebrospinal fluid)
an extensive neuropsychological battery. During subs
and one MRI. The PET scans are dependent on their d
TRIAD cohort uses a variety of tracers in their differe
accumulation in the brain. These tracers include [18F]M
[18F]AZD4694 , [11C]PBR or [18F]DPA, [18F]FEOBV
return for follow-up clinical and imagery visits 12 and
70%.

Results: Since 2017, the TRIAD registry has recruited
Enrolled in the TRIAD studies are individuals withou
impairment (n=75), sporadic and autosomal-dominant
(n=27) and individuals under evaluation (n=39).

Conclusion: TRIAD cohort presents a distinct opport
Alzheimer’s disease with resources ready to uphold th
diagnosing and measuring disease progression.

Keywords: biomarkers, cohort, diagnosis

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logy using multiparametric PET
ort

A. Pascoal1,2, Andrea Benedet1,2, Min Su
herriault1,2, Emilie Thomas1,2, Melissa Savard1,2,
Celluci1,2, Nesrine Rahmouni1,2, Guylaine
ica Shin1,2, Paolo Vitali1,2, Serge Gauthier1,3,

QC, Canada
nada
g and Dementia (TRIAD) cohort aims at describing
athophysiological processes as drivers of dementia. As
ing, TRIAD focuses on advanced personalized and
ives include understanding the interactions between
brain atrophy and cognitive decline, as well as the
depletion as mediators of cognitive decline.
ns with a telephone screening ensuring the
approved consent form where they agree to donate
) at the first on-site visit. The second visit consists of
sequent visits, participants undergo three PET scans
diagnosis and the project in which they are enrolled.
ent projects to detect the presence of different protein
MK6240, [18F]AV1451, [18F]PI2620 and [18F]RO948,
V [11C]MRT and [11C]UCB-J. TRIAD participants
d 24 months after baseline with a retention rate of

d 1,285 people and has enrolled 576 participants.
ut cognitive impairment (n=345), with mild cognitive
t Alzheimer’s disease (n=90), atypical dementia

tunity to further understand the progression of
he use of affordable biomarkers, capable of

44

Tissot, Cécile

P49: Interaction between amyloid and
the Alzheimer’s disease spectrum

Cécile Tissot1,2,3, Min Su Kang1,2, Andrea Bene
Pascoal1,2, Mira Chamoun1,2,3, Joseph Therriault
Sulantha Mathotaarachchi1,2,3, Emilie Thomas1,2

1McGill University, Montreal, QC, Canada
2Translational Neuroimaging Laboratory, Montreal, Q
3Douglas Hospital Research Center, Verdun, QC, Can

Introduction: The Apathy Inventory is a rating scale
globally. This neuropsychiatric symptom is the most c
disease (AD), and it causes a great burden on diseased
been closely related to cerebrospinal fluid levels of ne
of pathologies is still unclear. Here we test the interac
brain with apathy, along the AD spectrum.

Methods: We assessed 59 individuals (38 cognitively
with [11C]PBR28-neuroinflammation positron-emissio
PET. [11C]PBR28 and [18F]AZD4694 uptake value rat
reference region and were calculated 0-90 min post-in
voxel-based regression model evaluated the relationsh
[11C]PBR28 with Apathy Inventory scores. The mode
diagnoses of the participants.

Results: We found a strong positive correlation betwe
with apathy. The most impacted regions were the med
prefrontal cortex, as well as the anterior nucleus of the

Conclusion: These preliminary results show an intera
amyloid and neuroinflammation, that potentiate apath
regulation, such as the medialfrontal cortex. On the ot
indicators of a poorer connection between different br
symptom. This study corroborates with previous findi
to apathy. The limbic dysfunctions causing apathy mi
and neuroinflammation along the AD spectrum.

14

d neuroinflammation on apathy along

edet1,2,3, Nesrine Rahmouni1,2, Tharick A.
t1,2,3, Firoza Lussier1,2,3, Melissa Savard1,2,
2, Serge Gauthier1,2,3, Pedro Rosa-Neto1,2,3

QC, Canada
nada
given to informants in order to assess levels of apathy
common noncognitive symptom in Alzheimer’s
d individuals and their caregivers. Even though it has
euroinflammation and amyloid, the interactive effect
ction between amyloid and neuroinflammation in the

y unimpaired, 15 mild-cognitive impairment, 6 AD)
on tomography (PET) and [18F]AZD4694-amyloid
tios (SUVRs) used the cerebellum grey matter as the
njection and 40-70 min post-injection respectively. A
hip between the interaction of [18F]AZD4694 and
el’s covariates were age, gender, education and

een the interaction of [18F]AZD4694 and [11C]PBR28
dialfrontal cortex, in the superior portion and
e thalamus.
active link between two pathophysiologies of AD,
hy. The regions impacted are involved in behavioral
ther hand, the results found in the thalamus might be
rain regions, leading to an increase of apathetic
ings that amyloid and neuroinflammation are related
ight thus be due to the interactive effect of amyloid

45

Keywords: apathy, neuroinflammation, amyloid, inter
14

raction
46

Tissot, Cécile

P50: Neuropsychiatric symptoms in co
correlated with tau deposition

Cécile Tissot1,2,3, Joseph Therriault1,2,3, Tharick
Lussier1,2,3, Melissa Savard1,2, Sulantha Mathota
Thomas1,2,3, Pedro Rosa-Neto1,2,3, Serge Gauthie

1McGill University, Montreal, QC, Canada
2Translational Neuroimagery Laboratory, Montreal, Q
3Douglas Hospital Research Center, Verdun, QC, Can

Introduction: Neuropsychiatric Inventory-Questionn
assess the participant’s neuropsychiatric symptoms (N
informant. Although NPS have been closely related to
Alzheimer’s disease (AD) pathophysiology, the relatio
neurodegeneration pathologies is still unclear. Here w
brain and NPS in cognitively impaired (CI) individual

Methods: 61 CI individuals (MCI = 34, AD = 27) und
amyloid [18F]AZD4694 and tau [18F]MK-6240. [18F]A
value ratios (SUVRs) used the cerebellum grey matter
40-70 min and 90-110 min post-injection, respectively
were also conducted. A voxel based regression model
of a biomarker, using [18F]MK6240 or [18F]AZD4694
model’s covariates were age, gender and years of educ
analyzing [18F]MK6240, and for tau deposition when

Results: We found strong positive correlation betwee
regions were the precuneus, the hippocampal formatio
any correlation between NPI-Q and [18F]AZD4694 up

Conclusion: These preliminary results show a compe
behavioral disturbances, such as the frontal cortex, as
precuneus and hippocampus. This corroborates with th
and behavioral symptoms than other AD pathophysiol
with neurofibrillary tangles, it is thus important to ass

14

ognitively impaired individuals are

A. Pascoal1,2,3, Mira Chamoun1,2, Firoza
aarachchi1,2, Andrea Benedet1,2,3, Emilie
er1,3

QC, Canada
nada
naire (NPI-Q) is a survey addressed to informants to
NPS) and their impact on the participant and their
o the clinical progression to dementia in carriers of
onship between NPS and brain amyloid, tau and
we test the relationship between tau aggregates in the
ls.
derwent positron emission tomography (PET)
AZD4694 and [18F]MK-6240 standardized uptake
r as the reference region and were calculated between
y. Analyses with voxel-based morphometry (VBM)
l evaluated the relationship between the accumulation
4 PET scans, VBM, and the NPI-Q scores. The
cation. We corrected for amyloid deposition when
analyzing [18F]AZD4694.
en NPI-Q and [18F]MK6240. The most impacted
on, and the frontal cortex. However, we did not find
ptake nor VBM.
elling correlation between NPS and regions related to
well as the first regions impacted in AD, meaning the
he idea that tau is more closely related with cognitive
logies. This study demonstrates that NPS correlate
sess them, with the help of a reliable informant.

47

Keywords: neuropsychiatric symptoms, tau, alzheimer
14

r’s disease
48

Wang, Yi-Ting

P51: Association between [18F]NAV46
fluid biomarkers across the spectrum

Yi-Ting Wang1,2, Tharick Pascoal1,2, Joseph The
Melissa Savard1,2, Min Su Kang1,2, Cecile Tisso

1Translational Neuroimaging Lab, Montreal, QC, Can
2McGill Center for Studies in Aging, Montreal, QC, C

Background: [11C]PiB and [18F]Florbetapir are by far
Standardised uptake value ratios (SUVRs) of both trac
and they showed similar classification accuracy and d
focuses on plasma biomarkers due to its potential to b
measure. [18F]NAV4694, a third generation Aβ PET r
characteristics nearly identical to those of [11C]PiB. In
binding support its utility in both research and clinical
[18F]NAV4694 PET Aβ measures and AD fluid bioma
Objectives: (1) Validate the association between [18F
(2) Investigate the relationship between [18F]NAV469

Methods: This was a cross-sectional study in 106 sub
normal controls (n=54) and young healthy controls (n
Studies in Aging, Canada. Associations were tested be
biomarkers.
Results: [18F]NAV4694 PET global SUVR showed st
(P<0.001, Pearson's r=0.78), and moderate correlation
(P<0.001, Pearson's r: CSF Aβ42=0.45, CSF pTau=0.
measures demonstrated linear relationships with CSF
level.

Conclusion: Our results support the high concordance
SUVRs, especially when CSF Aβ42/pTau ratio was u
CSF biomarkers generally correlate better with [18F]N
properly, plasma pTau could be a promising biomarke
course of AD.

14

694 PET amyloid-β measures and
of Alzheimer's disease

erriault1,2, Andréa Benedet1,2, Firoza Lussier1,2,
ot1,2, Serge Gauthier1,2, Pedro Rosa-Neto1,2

nada
Canada

r the most well-studied amyloid PET radioligands.
cers are highly correlated with CSF Aβ biomarkers,
diagnostic agreement. Recently, intensive research
be applied in routine clinical settings as a screening
radiotracer, has been validated to display imaging
n addition, the low white matter and high cortical
l settings. However, the association between
arkers has not yet been studied in living humans.
F]NAV4694 PET Aβ SUVR and CSF Aβ biomarkers
94 PET SUVR, CSF and plasma biomarkers
bjects with AD (n=10), MCI (n=22), cognitively
n=20) from the TRIAD cohort at McGill Centre for
etween [18F]NAV4694 PET SUVRs, CSF and plasma

trong correlation with CSF Aβ42/pTau ratio
n with CSF Aβ42, CSF pTau and plasma pTau181
.58, plasma pTau181=0.6). [18F]NAV4694 PET Aβ
Aβ42, CSF Aβ42/40, CSF pTau and plasma pTau181

e between CSF biomarkers and [18F]NAV4694 PET
used. Furthermore, these findings note that although
NAV4694 PET imaging biomarkers, when modelling
er for monitoring disease progression throughout the

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