Year: 2019
Type: dissertation
Study design: Observational Study
Abstract: Despite well-described temporal staging, the relationships between Alzheimer’s disease (AD) biomarkers remain unclear. First, using cross-lagged panel models, we examined the reciprocal longitudinal influences between biomarkers of amyloid-beta (Aβ) and phospho-tau (p-tau), hallmark proteins that accumulate in the AD brain, in both asymptomatic/presymptomatic elderly (HC), and in subjects with AD or mild cognitive impairment (AD/MCI) over 48 months. Second, reciprocal relationships between brain Aβ deposition and white matter hyperintensity volumes (WMH), presumed to be of vascular origin, were examined. In HC, cerebrospinal fluid (CSF) Aβ changes led to increased Aβ deposition and increased CSF p-tau concentrations, and CSF p-tau exacerbated Aβ deposition. In contrast, in AD/MCI, CSF p-tau exacerbated Aβ deposition, but p-tau progressed independently of Aβ biomarkers. WMH led to Aβ deposition in HC, while in MCI, it was Aβ deposition that predicted incident WMH. Processes underlying CSF Aβ changes, and cerebrovascular disease, may initiate the amyloid cascade in presymptomatic stages.
Source: TSpace (University of Toronto)
Author: Saffire H. Krance
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3157799052