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.