Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer’s disease

The accumulation of neurofibrillary tangles in Alzheimer’s disease (AD) propagates with characteristic spatiotemporal patterns which follow brain network connections, implying trans-synaptic transmission of tauopathy. Since misfolded tau has been shown to transmit across synapses in AD animal models, we hypothesized that synapses in AD patients may contain misfolded tau. By immunofluorescence imaging of bipartite synapses from AD subjects, we detected tau protein in 38.4% of presynaptic and 50.9% of postsynaptic terminals. The pre/post distribution for hyperphosphorylated tau was 26.9%/30.7%, and for misfolded tau 18.3%/19.3%. In the temporal cortex, microscopic aggregates of tau, containing ultra-stable oligomers, were estimated to accumulate within trillions of synapses, outnumbering macroscopic tau aggregates such as tangles by 10000 fold. Non-demented elderly also showed considerable synaptic tau hyperphosphorylation and some misfolding, implicating the synapse as one of the first subcellular compartments affected by tauopathy. Misfolding of tau protein appeared to occur in situ inside synaptic terminals, without mislocalizing or mistrafficking. Misfolded tau at synapses may represent early signs of neuronal degeneration, mediators of synaptotoxicity, and anatomical substrates for transmitting tauopathy, but its actual role in these processes remain to be elucidated.

• Publication year

  2014

• Venue

  Acta Neuropathologica Communications

• Publication date

  2014-10-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s40478-014-0146-2PMID 25330988PMCID 4209049
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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