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Abstract Details

Distribution of Hippocampal Tau Pathology in Amnestic and Non-Amnestic Forms of Alzheimer’s Disease
Aging, Dementia, and Behavioral Neurology
S34 - Aging and Dementia: Risk Factors, Biomarkers, and Neuropathology (2:28 PM-2:39 PM)
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Traditional AD tau Braak staging, based largely on the presence/absence of tau in serial autopsies, described a stereotypical progression of tau pathology in HIPPsf. Many younger AD patients present with non-amnestic syndromes (naAD) during life, suggesting relative sparing of the hippocampus, but patterns of tau in HIPPsf in these patients are understudied. We used digital pathology to test the hypotheses that 1) severity of tau pathology measured by digital pathology in HIPPsf will reflect traditional Braak staging in aAD and 2) naAD patients have lower hippocampal tau than aAD.

 To compare the distribution and severity of tau pathology in hippocampal subfields (HIPPsf) between amnestic (aAD) and non-amnestic Alzheimer’s Disease (naAD).

We selected autopsy-confirmed naAD (n=41) and an age/sex-matched autopsy aAD reference cohort (n=40) for study. Hippocampal sections were stained for phosphorylated-tau (AT8), scanned on a digital slide scanner and digital images analyzed using HALO software. Hippocampal subfields [Entorhinal Cortex (ERC) and Cornu Ammonis (CA) regions: CA2/3, CA1/Subiculum and CA4/dentate gyrus (DG)] were manually segmented using cytoarchitectural features according to a previously validated approach and percent-area occupied (%AO) tau measured in each subfield. We used a linear mixed-effects model to test HIPPsf regional and clinical-group differences in ln-transformed %AO tau.

We found a significant effect of subfield region, with lower tau %AO in later-affected subregions, including  CA2/3 and CA4/DG compared to early-affected ERC (β=-0.5,-1.6, p<0001), whereas earlier-affected CA1/Subiculum had similar high-level tau %AO to ERC (β=-0.03, p>0.1). We also found a significant “clinical group x subfield” interaction, with lower tau %AO in naAD in CA4/DG (β=-0.5, p<0.04).

Digital measure of tau pathology in postmortem HIPPsf appear to recapitulate traditional Braak stages in aAD, where early regions (CA1/Subiculum and ERC) have higher tau than later-affected subfields (CA 2/3, CA4/DG). Tau pathology in naAD may relatively spare later-stage HIPPsf.

Authors/Disclosures
David Irwin, MD (University of Pennsylvania)
PRESENTER
The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali.
Simon Miller No disclosure on file
Jeffrey S. Phillips, PhD (Penn FTD Center, Department of Neurology) No disclosure on file
No disclosure on file
Claire S. Peterson Ms. Peterson has nothing to disclose.
No disclosure on file
John Q. Trojanowski, MD, PhD (University of PA School of Med) Dr. Trojanowski has nothing to disclose.
David A. Wolk, MD, FAAN (University of Pennsylvania) Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
No disclosure on file
Murray Grossman, MD, FAAN (University of Pennsylvania) Dr. Grossman 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 Neurology. The institution of Dr. Grossman has received research support from NIH.