학술논문
Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease
Document Type
article
Author
Sanaz Arezoumandan; Katheryn A.Q. Cousins; Daniel T. Ohm; MaKayla Lowe; Min Chen; James Gee; Jeffrey S. Phillips; Corey T. McMillan; Kelvin C. Luk; Andres Deik; Meredith A. Spindler; Thomas F. Tropea; Daniel Weintraub; David A. Wolk; Murray Grossman; Virginia Lee; Alice S. Chen‐Plotkin; Edward B. Lee; David J. Irwin
Source
Annals of Clinical and Translational Neurology, Vol 11, Iss 3, Pp 673-685 (2024)
Subject
Language
English
ISSN
2328-9503
Abstract
Abstract Objective Alzheimer's disease neuropathologic change and alpha‐synucleinopathy commonly co‐exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta‐amyloid compared to alpha‐synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia. Methods We used digital histology to measure percent area‐occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha‐synucleinopathy, and a co‐pathology group with both Alzheimer's and alpha‐synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features. Results There were lower levels of tau pathology (β = 1.86–2.96, p