Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer's disease

Abstract

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.

Figure 1

Bright field photomicrographs of nucleus basalis cholinergic basal forebrain (CBF) neurons dual stained for pS422 (brown) and TOC1 (dark blue) in NCI (A), MCI (B) and AD (D). Arrows indicate single pS422 neurons. Laser-confocal dual immunoflouresence (E) showing TOC1 (green), pS422 (red) and merged images of CBF neurons in MCI. Scale bar in D is same for A-C and in E = 50μm.