title: Increased levels of granular tau oligomers: an early sign of brain aging and Alzheimer's disease.
abstract: Development of neurofibrillary tangles (NFTs) is a pathological hallmark in various neurodegenerative disorders including Alzheimer's disease (AD). Recently, we identified a granular tau oligomer having a pre-filamentous structure. To determine the role of this oligomer in NFT formation, we quantified the amount of granular tau oligomer in 21 frontal cortex samples, each displaying varying degrees of Braak-staged NFT pathology. Here we report that granular tau oligomer levels in frontal cortex were significantly increased, even in brains displaying Braak-stage I neuropathology, a stage at which clinical symptoms of AD and NFTs in frontal cortex are believed to be absent. This suggests that increases in granular tau oligomer levels occur before NFTs form and before individuals manifest clinical symptoms of AD. Increased granular tau oligomer levels, therefore, may lead to NFT formation in frontal cortex, eventually leading to the development of AD. Thus, increases in granular tau oligomer levels may represent a very early sign of NFT formation and AD.
authors.affiliation: Lab for Alzheimer's Disease, Brain Science Institute, RIKEN, 2-1 Hirosaswa, Wako, Saitama 351-0198, Japan.
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Maeda
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sahara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikai
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins