Aberrant Synaptic PTEN in Symptomatic Alzheimer’s Patients May Link Synaptic Depression to Network Failure

Marta Díaz González, Assaf Buberman, Miguel Morales, Isidro Ferrer, Shira Knafo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In Alzheimer’s disease (AD), Amyloid β (Aβ) impairs synaptic function by inhibiting long-term potentiation (LTP), and by facilitating long-term depression (LTD). There is now evidence from AD models that Aβ provokes this shift toward synaptic depression by triggering the access to and accumulation of PTEN in the postsynaptic terminal of hippocampal neurons. Here we quantified the PTEN in 196,138 individual excitatory dentate gyrus synapses from AD patients at different stages of the disease and from controls with no neuropathological findings. We detected a gradual increase of synaptic PTEN in AD brains as the disease progresses, in conjunction with a significant decrease in synaptic density. The synapses that remain in symptomatic AD patients are more likely to be smaller and exhibit fewer AMPA receptors (AMPARs). Hence, a high Aβ load appears to strongly compromise human hippocampal synapses, as reflected by an increase in PTEN, inducing a loss of AMPARs that may eventually provoke synaptic failure and loss.

Original languageEnglish
Article number683290
JournalFrontiers in Synaptic Neuroscience
Volume13
DOIs
StatePublished - 11 May 2021

Keywords

  • PSD-95
  • cognition
  • hippocampus
  • human
  • plasticity
  • synaptosomes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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