Digital Histological Study of Neocortical Grey and White Matter Tau Burden Across Tauopathies

David G. Coughlin*, Annie Hiniker, Claire Peterson, Yongya Kim, Sanaz Arezoumandan, Lucia Giannini, Donald Pizzo, Daniel Weintraub, Andrew Siderowf, Irene Litvan, Robert A. Rissman, Douglas Galasko, Lawrence Hansen, John Q. Trojanowski, Edward Lee, Murray Grossman, David Irwin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

3R/4R-tau species are found in Alzheimer disease (AD) and ∼50% of Lewy body dementias at autopsy (LBD+tau); 4R-tau accumulations are found in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Digital image analysis techniques can elucidate patterns of tau pathology more precisely than traditional methods but repeatability across centers is unclear. We calculated regional percentage areas occupied by tau pathological inclusions from the middle frontal cortex (MFC), superior temporal cortex (STC), and angular gyrus (ANG) from cases from the University of Pennsylvania and the University of California San Diego with AD, LBD+tau, PSP, or CBD (n = 150) using QuPath. In both cohorts, AD and LBD+tau had the highest grey and white matter tau burden in the STC (p ≤ 0.04). White matter tau burden was relatively higher in 4R-tauopathies than 3R/4R-tauopathies (p < 0.003). Grey and white matter tau were correlated in all diseases (R2=0.43-0.79, p < 0.04) with the greatest increase of white matter per unit grey matter tau observed in PSP (p < 0.02 both cohorts). Grey matter tau negatively correlated with MMSE in AD and LBD+tau (r = -4.4 to -5.4, p ≤ 0.02). These data demonstrate the feasibility of cross-institutional digital histology studies that generate finely grained measurements of pathology which can be used to support biomarker development and models of disease progression.

Original languageEnglish
Pages (from-to)953-964
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume81
Issue number12
Early online date21 Oct 2022
DOIs
Publication statusPublished - 1 Dec 2022

Bibliographical note

Funding Information:
This work was supported by grants from the American Academy of Neurology/American Brain Foundation/Parkinson's Foundation (2059), TL1TR001880, National Institute on Aging P30AG072979 (formerly AG010124), AG043503, AG062429, P01-AG066597 and National Institute on Neurological Disease and Stroke NS088341 and NS120038. Data were contributed to this study by the Center on Alpha-synuclein Strains in Alzheimer Disease & Related Dementias at the University of Pennsylvania Perelman School of Medicine (U19 AG062418, JQT-PI) and the former Morris K. Udall Center at the University of Pennsylvania Perelman School of Medicine (P50 NS053488, JQT-PI).

Publisher Copyright:
© 2022 The Author(s).

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