Digital Histological Study of Neocortical Grey and White Matter Tau Burden Across Tauopathies
- 21 October 2022
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 81 (12), 953-964
- https://doi.org/10.1093/jnen/nlac094
Abstract
3R/4R-tau species are found in Alzheimer disease (AD) and similar to 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 (R-2=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.Keywords
This publication has 97 references indexed in Scilit:
- National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approachActa Neuropathologica, 2011
- Rapid eye movement sleep behavior disorder and subtypes in autopsy‐confirmed dementia with Lewy bodiesMovement Disorders, 2011
- Disrupted thalamocortical connectivity in PSP: A resting-state fMRI, DTI, and VBM studyParkinsonism & Related Disorders, 2011
- Neuropathology of Frontotemporal Lobar Degeneration-Tau (FTLD-Tau)Journal of Molecular Neuroscience, 2011
- Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?Brain, 2011
- Clinicopathological correlations in corticobasal degenerationAnnals of Neurology, 2011
- Neuropathology of variants of progressive supranuclear palsyCurrent Opinion in Neurology, 2010
- Dementia with Lewy bodies and Alzheimer diseaseNeurology, 2010
- Parkinson Disease With DementiaAlzheimer Disease & Associated Disorders, 2009
- Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson's syndromeBrain, 2007