Digital Histological Measurements Show a Range of Values Within Traditional Pathological Metrics of AD-related Tau Pathology (P3-6.002)

Abstract

<h3>Objective:</h3> To examine spectrum of neocortical tau burden using digital histological methods in Alzheimer’s disease (AD) and Lewy Body Disease (dementia with Lewy bodies and Parkinson’s disease) with AD co-pathology (LBD+AD) with high Braak tau stages. <h3>Background:</h3> Neuropathological assessment remains gold-standard for diagnosing and staging neurodegenerative diseases. Digital histological assessment may capture a spectrum of pathological burden not easily demonstrated by traditional methods. <h3>Design/Methods:</h3> Cases from UC-San Diego (UCSD) and University of Pennsylvania (UPenn) with AD (UCSD:15, UPenn:33) and LBD+AD (UCSD:7, UPenn:10) with Braak tau stages V and VI (B3) had middle frontal cortex (MFC), superior temporal cortex (STC), and angular gyrus (ANG) immunohistochemically stained for pathological tau inclusions (AT8) and whole-slide images analyzed for tau %area occupied (tau%AO) using QuPath image analysis software. Natural-log tau%AO values were compared between ordinal severity scores (0–3), Braak stages, and between AD and LBD+AD in each region using ANOVA and t-tests. <h3>Results:</h3> In both cohorts, here were significant increases in tau%AO across blinded regional ordinal severity scores (UCSD F=28.4, p&lt;0.001, UPenn F=236, p&lt;0.001). All regions had higher tau%AO in Braak VI cases than Braak V in the UCSD cohort (p&lt;0.02). The STC harbored the highest tau%AO values in AD and LBD+AD. AD had higher tau%AO than LBD+AD in every region (MFC, STC, ANG, neocortical average: t=2.2–4.3, p&lt;0.03). <h3>Conclusions:</h3> Digital histological measurements recapitulate aspects of known patterns of AD-related tau pathology but reveal a range of pathological burden within current grading and staging systems. These methods may have relevance for ongoing biomarker development and modeling disease using human histology. <b>Disclosure:</b> The institution of Dr. Coughlin has received research support from American Academy of Neurology. The institution of Dr. Coughlin has received research support from NIA. The institution of Dr. Coughlin has received research support from NINDS. Mr. Kim has nothing to disclose. Ms. Arezoumandan has nothing to disclose. Ms. Peterson has nothing to disclose. Anne Hiniker has nothing to disclose. Larry Hansen has nothing to disclose. Dr. Rissman has nothing to disclose. Donald Pizzo has nothing to disclose. Edward Lee has nothing to disclose. Dr. Irwin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Denali Therapeutics. The institution of Dr. Irwin has received research support from NIH.