Synaptic resilience is associated with maintained cognition during ageing

Declan King, Kris Holt, Jamie Toombs, Xin He, Owen Dando, Judy Okely, Jamie Rose, Ciaran Gunn, Adele Correia, Carmen Montero, Jane Tulloch, Douglas Lamont, Adele Taylor, Sarah Harris, Paul Redmond, Simon R. Cox, Christopher Henstridge, Ian J Deary, Colin Smith, Tara Spires-Jones

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Introduction
It 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.

Methods
We 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.

Results
Synaptic 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.

Discussion
Efficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.
Original languageEnglish
JournalAlzheimer's & Dementia: The Journal of the Alzheimer's Association
Early online date22 Dec 2022
DOIs
Publication statusE-pub ahead of print - 22 Dec 2022

Fingerprint

Dive into the research topics of 'Synaptic resilience is associated with maintained cognition during ageing'. Together they form a unique fingerprint.

Cite this