Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer's disease
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Updated: May 7, 2026

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Elliott J Mufson1, Sarah Ward, Lester Binder
1Department of Neurological Sciences, Rush University Medical Center, Chicago, Ill., USA.
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.
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