Proteomic profiling of primate synapses during normal healthy ageing

Normal mammalian brain ageing is characterised by the selective loss of discrete populations of dendritic spines and synapses, particularly affecting neuroanatomical regions such as the hippocampus. Although previous investigations have quantified this morphologically, the molecular pathways orchestrating preferential synaptic vulnerability remain to be elucidated. Using quantitative proteomics and healthy rhesus macaque and human patient brain regional tissues, we have profiled the temporal expression of the synaptic proteome throughout the adult lifespan in differentially vulnerable brain regions. Comparative profiling of hippocampal (age-vulnerable) and occipital cortex (age-resistant) synapses revealed discrete and dynamic alterations in the synaptic proteome, which appear unequivocally conserved between species. The generation of these unique and important datasets will aid in delineating the molecular mechanisms underpinning primate brain ageing, in addition to deciphering the regulatory biochemical cascades governing neurodegenerative disease pathogenesis.