Differential expression of tau species and the association with cognitive decline and synaptic loss in Alzheimer's disease. Issue 9 (7th December 2021)

• Record Type: Journal Article
• Authors: Saroja, Sivaprakasam R.; Sharma, Abhijeet; Hof, Patrick R.; Pereira, Ana C.
• Is Part Of: Alzheimer's & dementia. Volume 18:Issue 9(2022)
• Page Start: 1602
• Page End: 1615
• Publication Date: 2021-12-07
• Subjects: Alzheimer's disease -- cognitive impairment -- extracellular vesicles and Serpina3n -- neurodegeneration -- synaptic loss -- tau pathology; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12518
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Pathological tau proteins in patients with Alzheimer's disease (AD) mainly accumulate in the form of neurofibrillary tangles (NFTs) and neuritic plaques (NPs). However, the molecular properties of tau species present in NFTs and NPs are not known. We tested the hypothesis that tau species within NFT‐predominant tissue (NFT_AD) are distinct and more toxic than those in NP‐predominant tissue (NP_AD). We analyzed the tau species from post mortem prefrontal cortical brains of NFT_AD and NP_AD. Compared to NP_AD, NFT_AD displayed highly phosphorylated tau oligomers, possessed tau oligomers in extracellular vesicles, and the 3‐repeat (3R) and 4‐repeat (4R) isoforms were differentially expressed between the groups. Comparison of tau proteins isolated from NFT‐ versus NP‐AD subjects demonstrated higher tau seeding activity in NFT subjects and a greater degree of inducing synaptic loss in cultured neurons. We propose that tau species from NFT‐predominant tissues possess greater levels of degenerative properties, thereby causing synaptic loss and cognitive decline.