Accurate digital quantification of tau pathology in progressive supranuclear palsy.

Autor: Pansuwan T; Department of Clinical Neurosciences, Cambridge University Centre for Parkinson-Plus, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ, UK. tp500@cam.ac.uk., Quaegebeur A; Department of Clinical Neurosciences, Cambridge University Centre for Parkinson-Plus, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Kaalund SS; Centre for Neuroscience and Stereology, Bispebjerg University Hospital, Copenhagen, Denmark., Hidari E; Department of Clinical Neurosciences, Cambridge University Centre for Parkinson-Plus, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ, UK., Briggs M; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Rowe JB; Department of Clinical Neurosciences, Cambridge University Centre for Parkinson-Plus, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK., Rittman T; Department of Clinical Neurosciences, Cambridge University Centre for Parkinson-Plus, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2023 Nov 09; Vol. 11 (1), pp. 178. Date of Electronic Publication: 2023 Nov 09.
DOI: 10.1186/s40478-023-01674-y
Abstrakt: The development of novel treatments for Progressive Supranuclear Palsy (PSP) is hindered by a knowledge gap of the impact of neurodegenerative neuropathology on brain structure and function. The current standard practice for measuring postmortem tau histology is semi-quantitative assessment, which is prone to inter-rater variability, time-consuming and difficult to scale. We developed and optimized a tau aggregate type-specific quantification pipeline for cortical and subcortical regions, in human brain donors with PSP. We quantified 4 tau objects ('neurofibrillary tangles', 'coiled bodies', 'tufted astrocytes', and 'tau fragments') using a probabilistic random forest machine learning classifier. The tau pipeline achieved high classification performance (F1-score > 0.90), comparable to neuropathologist inter-rater reliability in the held-out test set. Using 240 AT8 slides from 32 postmortem brains, the tau burden was correlated against the PSP pathology staging scheme using Spearman's rank correlation. We assessed whether clinical severity (PSP rating scale, PSPRS) score reflects neuropathological severity inferred from PSP stage and tau burden using Bayesian linear mixed regression. Tufted astrocyte density in cortical regions and coiled body density in subcortical regions showed the highest correlation to PSP stage (r = 0.62 and r = 0.38, respectively). Using traditional manual staging, only PSP patients in stage 6, not earlier stages, had significantly higher clinical severity than stage 2. Cortical tau density and neurofibrillary tangle density in subcortical regions correlated with clinical severity. Overall, our data indicate the potential for highly accurate digital tau aggregate type-specific quantification for neurodegenerative tauopathies; and the importance of studying tau aggregate type-specific burden in different brain regions as opposed to overall tau, to gain insights into the pathogenesis and progression of tauopathies.
(© 2023. The Author(s).)
Databáze: MEDLINE
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