{"DOI":"10.1101/2022.05.04.22274679","abstract":"ABSTRACT\n \n INTRODUCTION\n It remains unclear why age increases risk of Alzheimer's disease and why\n some people experience age-related cognitive decline in the absence of\n dementia. Here we test the hypothesis that resilience to molecular changes\n in synapses contribute to healthy cognitive ageing.\n \n \n METHODS\n We examined post-mortem brain from people in mid-life (n=15), healthy\n ageing with either maintained cognition (n=8) or lifetime cognitive decline\n (n=7), and Alzheimer's disease (n=13). Synapses were examined with high\n resolution imaging, proteomics, and RNA sequencing. Stem cell-derived\n neurons were challenged with Alzheimer's brain homogenate.\n \n \n RESULTS\n Synaptic pathology increased, and expression of genes involved in\n synaptic signalling decreased between mid-life, healthy ageing and\n Alzheimer's. In contrast, brain tissue and neurons from people with\n maintained cognition during ageing exhibited decreases in synaptic\n signalling genes compared to people with cognitive decline.\n \n \n DISCUSSION\n Efficient synaptic networks without pathological protein accumulation\n may contribute to maintained cognition during ageing.\n ","author":[{"family":"King","given":"Declan"},{"family":"Holt","given":"Kris"},{"family":"Toombs","given":"Jamie"},{"family":"He","given":"Xin"},{"family":"Dando","given":"Owen"},{"family":"Okely","given":"J. A."},{"family":"Rose","given":"Jamie"},{"family":"Gunn","given":"Ciaran"},{"family":"Correia","given":"Adele"},{"family":"Montero","given":"Carmen"},{"family":"Tulloch","given":"Jane"},{"family":"Lamont","given":"Douglas"},{"family":"Taylor","given":"Adele M"},{"family":"Harris","given":"Sarah E"},{"family":"Redmond","given":"Paul"},{"family":"Cox","given":"Simon R"},{"family":"Henstridge","given":"Christopher M"},{"family":"Deary","given":"Ian J"},{"family":"Smith","given":"Colin"},{"family":"Spires-Jones","given":"Tara L"}],"id":"unknown","issued":{"date-parts":[[2022,5,7]]},"publisher":"Cold Spring Harbor Laboratory","title":"Synaptic resilience is associated with maintained cognition during\n ageing","type":"post"}