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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Aging Research

Background:

  • Age is a primary risk factor for Alzheimer's disease (AD).
  • The reasons for age-related cognitive decline without dementia are not fully understood.
  • Synaptic molecular changes may underlie cognitive aging trajectories.

Purpose of the Study:

  • To investigate the role of synaptic resilience in healthy cognitive aging.
  • To compare molecular and pathological changes in synapses across different aging groups.

Main Methods:

  • Analysis of post-mortem brain tissue from mid-life, healthy aging (maintained cognition and cognitive decline), and Alzheimer's disease cohorts.
  • High-resolution imaging, proteomics, and RNA sequencing of synapses.
  • In vitro challenge of stem cell-derived neurons with AD brain homogenate.

Main Results:

  • Synaptic pathology increased, and synaptic signaling gene expression decreased from mid-life to Alzheimer's disease.
  • Individuals with maintained cognition during aging showed decreased synaptic signaling gene expression compared to those with cognitive decline.
  • Stem cell-derived neurons exposed to AD homogenate exhibited synaptic pathology.

Conclusions:

  • Efficient synaptic networks, independent of pathological protein buildup, are crucial for maintaining cognition during aging.
  • Synaptic resilience may be a key factor in preventing age-related cognitive decline and Alzheimer's disease.