학술논문
Global neuropathologic severity of Alzheimer’s disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels
Document Type
article
Author
Melissa E. Murray; Christina M. Moloney; Naomi Kouri; Jeremy A. Syrjanen; Billie J. Matchett; Darren M. Rothberg; Jessica F. Tranovich; Tiffany N. Hicks Sirmans; Heather J. Wiste; Baayla D. C. Boon; Aivi T. Nguyen; R. Ross Reichard; Dennis W. Dickson; Val J. Lowe; Jeffrey L. Dage; Ronald C. Petersen; Clifford R. Jack; David S. Knopman; Prashanthi Vemuri; Jonathan Graff-Radford; Michelle M. Mielke
Source
Molecular Neurodegeneration, Vol 17, Iss 1, Pp 1-14 (2022)
Subject
Language
English
ISSN
1750-1326
Abstract
Abstract Background Advances in ultrasensitive detection of phosphorylated tau (p-tau) in plasma has enabled the use of blood tests to measure Alzheimer’s disease (AD) biomarker changes. Examination of postmortem brains of participants with antemortem plasma p-tau levels remains critical to understanding comorbid and AD-specific contribution to these biomarker changes. Methods We analyzed 35 population-based Mayo Clinic Study of Aging participants with plasma p-tau at threonine 181 and threonine 217 (p-tau181, p-tau217) available within 3 years of death. Autopsied participants included cognitively unimpaired, mild cognitive impairment, AD dementia, and non-AD neurodegenerative disorders. Global neuropathologic scales of tau, amyloid-β, TDP-43, and cerebrovascular disease were examined. Regional digital pathology measures of tau (phosphorylated threonine 181 and 217 [pT181, pT217]) and amyloid-β (6F/3D) were quantified in hippocampus and parietal cortex. Neurotransmitter hubs reported to influence development of tangles (nucleus basalis of Meynert) and amyloid-β plaques (locus coeruleus) were evaluated. Results The strongest regional associations were with parietal cortex for tau burden (p-tau181 R = 0.55, p = 0.003; p-tau217 R = 0.66, p