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Abstract Details

Cross-sectional and longitudinal effects of APOE genotype on atrophy and tau burden in atypical Alzheimer’s disease
Aging, Dementia, Cognitive, and Behavioral Neurology
P9 - Poster Session 9 (5:30 PM-6:30 PM)
3-003

APOE ε4 is an important genetic risk variant for typical AD. While APOE ε4 influences brain volume and tau burden in typical AD, little is known about its influence on the neuroimaging metrics in atypical AD.

To assess relationships between apolipoprotein E (APOE) ε4, cross-sectional and longitudinal measures of brain volume and tau burden in atypical Alzheimer’s disease (AD), including logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA).

An atypical AD (all amyloid positive on PET) cohort of 140 patients (82 LPA and 58 PCA) were recruited by the Neurodegenerative Research Group and underwent MRI and [18F]flortaucipir PET. 45 patients had longitudinal imaging. Regional gray matter volumes and PET standardized uptake value ratios (SUVRs) were calculated and mixed linear models assessed the influence of APOE ε4 on regional metrics, correcting for age, sex and total intracranial volume.

In atypical AD (51% APOE ε4 carriers), APOE ε4 carriers had 4% smaller baseline hippocampal volumes (p=0.04), with a trend for 4% smaller amygdala volumes (p=0.05), versus non-carriers. Within LPA, carriers similarly had a trend for 4% smaller amygdala volumes versus non-carriers (p=0.09), although no differences in volume were observed between carriers and non-carriers in PCA. No differences in rates of atrophy were observed between carriers and non-carriers in atypical AD, LPA or PCA. For tau-PET, the hippocampus showed a trend for 6% greater baseline tau uptake (p=0.08), but 4% slower rates of tau accumulation (p=0.04), in atypical AD carriers versus non-carriers. Within PCA, carriers had 6% higher rates of tau accumulation in hippocampus (p=0.02) versus non-carriers. No differences in tau uptake or rate by APOE status were observed in LPA. 

APOE ε4 influences patterns of neurodegeneration and tau deposition in atypical AD by promoting more medial temporal involvement, although APOE status was not related to faster worsening in these regions.

Authors/Disclosures
Neha Atulkumar Singh, PhD (Mayo Clinic)
PRESENTER
Dr. Singh has nothing to disclose.
Nirubol Tosakulwong Nirubol Tosakulwong has nothing to disclose.
Jonathan Graff-Radford, MD, FAAN Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. Dr. Graff-Radford has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. The institution of Dr. Graff-Radford has received research support from NIH. The institution of Dr. Graff-Radford has received research support from Eisai.
Mary M. Machulda, PhD (Mayo Clinic) The institution of Dr. Machulda has received research support from NIH.
Stephen Weigand Stephen Weigand has nothing to disclose.
Nilufer Taner, MD, PhD, FAAN (Mayo Clinic) The institution of Dr. Taner has received research support from NIH.
Christopher Schwarz Christopher Schwarz has received personal compensation for serving as an employee of Mayo Clinic. The institution of Christopher Schwarz has received research support from NIH.
Matthew Senjem (Mayo Clinic) Matthew Senjem has received stock or an ownership interest from Align Technology, Inc.. Matthew Senjem has received stock or an ownership interest from Inovio Biomedical Corp.. Matthew Senjem has received stock or an ownership interest from Johnson & Johnson. Matthew Senjem has received stock or an ownership interest from Mesa Laboratories, Inc.. Matthew Senjem has received stock or an ownership interest from Nvidia Inc.. Matthew Senjem has received stock or an ownership interest from LHC Group, Inc.. Matthew Senjem has received stock or an ownership interest from Natus Medical Incorporated. Matthew Senjem has received stock or an ownership interest from Varex Imaging Corporation. Matthew Senjem has received personal compensation in the range of $100,000-$499,999 for serving as a IT Technical Specialist II with Mayo Clinic.
Clifford R. Jack, Jr., MD (Mayo Clinic) The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Val John Lowe, MD (Mayo Clinic) Dr. Lowe has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AVID Radiopharmaceutical. Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Inc. The institution of Dr. Lowe has received research support from AVID Radiopharmaceuticals.
Keith A. Josephs, Jr., MD, FAAN (Mayo Clinic) Dr. Josephs has nothing to disclose.
Jennifer Louise Whitwell, PhD (Mayo Clinic) Dr. Whitwell has nothing to disclose.