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July 29, 2026Brain Research BulletinOpen Access

Presenilin deficiency beyond amyloid: Lessons from presenilin 1/2 conditional double-knockout mice on synaptic failure, calcium dyshomeostasis, and inflammation-driven Alzheimer’s disease

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Authors

GYGuang YangXXXiao XuYXYing Xu

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Overview

Randomized trial investigates cognitive rescue and synaptic function in presenilin double-knockout mice, suggesting new therapeutic directions.

Key Points

  • This research aims to explore the effects of presenilin deficiency on synaptic function and inflammation-related mechanisms in Alzheimer's disease models.
  • Utilized presenilin 1/2 conditional double-knockout (PS cDKO) mice to analyze synaptic and inflammatory changes postnatally in forebrain neurons.
  • Conducted interventions targeting anti-inflammatory, cholinergic, and metabolic pathways to assess cognitive and plasticity outcomes in PS cDKO mice.
  • Investigated molecular pathways related to calcium microdomains and neuroinflammatory responses in presenilin-deficient models.
  • Found that presenilin deficiency leads to significant synaptic failures, including reduced presynaptic release probability and impaired NMDAR function.
  • Observed a marked increase in neuroinflammation characterized by cytokine surges and inflammasome activation that exacerbated synaptic impairment.
  • Demonstrated that cognitive and synaptic functions can be rescued through targeted interventions that do not engage amyloid pathways.

Cite This Study

Yang et al. (2026) studied this question.

synapsesocial.com/papers/6a69a24dc8da07d9defa5902https://doi.org/10.1016/j.brainresbull.2026.112057
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