title: Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease.
abstract: Recent demonstrations that the secretion, uptake, and interneuronal transfer of tau can be modulated by disease-associated tau modifications suggest that secretion may be an important element in tau-induced neurodegeneration. Here, we show that much of the tau secreted by M1C cells occurs via exosomal release, a widely characterized mechanism that mediates unconventional secretion of other aggregation-prone proteins (α-synuclein, prion protein, and β-amyloid) in neurodegenerative disease. Exosome-associated tau is also present in human CSF samples and is phosphorylated at Thr-181 (AT270), an established phosphotau biomarker for Alzheimer disease (AD), in both M1C cells and in CSF samples from patients with mild (Braak stage 3) AD. A preliminary analysis of proteins co-purified with tau in secreted exosomes identified several that are known to be involved in disease-associated tau misprocessing. Our results suggest that exosome-mediated secretion of phosphorylated tau may play a significant role in the abnormal processing of tau and in the genesis of elevated CSF tau in early AD.
authors: Department of Biological Sciences, University of Massachusetts, Lowell, Massachusetts 01854, USA.
authors: Sudad
authors: S
authors: Saman
authors: WonHee
authors: W
authors: Kim
authors: Mario
authors: M
authors: Raya
authors: Yvonne
authors: Y
authors: Visnick
authors: Suhad
authors: S
authors: Miro
authors: Sarmad
authors: S
authors: Saman
authors: Bruce
authors: B
authors: Jackson
authors: Ann C
authors: AC
authors: McKee
authors: Victor E
authors: VE
authors: Alvarez
authors: Norman C Y
authors: NC
authors: Lee
authors: Garth F
authors: GF
authors: Hall
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D010766:Phosphorylation / Q000235:genetics; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins