Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer's disease and other tauopathies.

ABSTRACT: The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH₂ -derived fragments of protein on synaptic dysfunction underlying neurodegenerative tauopathies, including Alzheimer's disease (AD). Here we show that sub-toxic doses of extracellular-applied human NH₂ tau 26-44 (aka NH ₂ htau) -which is the minimal active moiety of neurotoxic 20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma- acutely provokes presynaptic deficit in K⁺ -evoked glutamate release on hippocampal synaptosomes along with alteration in local Ca²⁺ dynamics. Neuritic dystrophy, microtubules

SUBMITTER: Florenzano F 

PROVIDER: S-EPMC5630290 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature