Synaptic resilience is associated with maintained cognition during ageing

IntroductionIt remains unclear why age increases risk of Alzheimer's disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in synapses contribute to healthy cognitive ageing. MethodsWe examined post-mortem brain tissue from people in mid-life (n = 15), healthy ageing with either maintained cognition (n = 9) or lifetime cognitive decline (n = 8), and Alzheimer's disease (n = 13). Synapses were examined with high resolution imaging, proteomics, and RNA sequencing. Stem cell-derived neurons were challenged with Alzheimer's brain homogenate. ResultsSynaptic pathology increased, and expression of genes involved in synaptic signaling decreased between mid-life, healthy ageing and Alzheimer's. In contrast, brain tissue and neurons from people with maintained cognition during ageing exhibited decreases in synaptic signaling genes compared to people with cognitive decline. DiscussionEfficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.

Automated summary

This study examines the contribution of synaptic molecular changes to age-related cognitive decline and finds that synaptic pathology and gene expression related to synaptic signaling are associated with Alzheimer's disease.