Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer's disease
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of extracellular amyloid-β peptide and intracellular tau. Here, we review data suggesting that prefibrillar tau oligomers mediate cognitive decline early in the disease. Objective: It was our aim to study the presence of tau-positive pretangle neurons and correlate findings with cognitive test scores. Methods: Pretangle antibodies (TOC1 and pS422) were applied to tissue containing cholinergic basal forebrain neurons from people who died with a premortem clinical diagnosis of no cognitive impairment, mild cognitive impairment and AD. Results: Data lend support to the concept that tau oligomers are the toxic form of tau, that non-fibillar tau relates to cognitive dysfunction and that the earliest pretangle pathology occurs in neuritic processes. Conclusions: Clinicopathological findings highlight the importance of studying tau modifications in neuronal soma and neuritic processes, which may be the earliest pathological lesions that correlate with cognitive status. © 2013 S. Karger AG, Basel.
Alzheimer's disease, Fibrillar aggregates, Mild cognitive impairment, Oligomers, Tau
Digital Object Identifier (DOI)
Mufson, Elliott J.; Ward, Sarah; and Binder, Lester, "Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer's disease" (2014). Translational Neuroscience. 1918.