@article{9154228142464c85bb6f615664ede226,
title = "Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging",
abstract = "Normal mammalian brain aging is characterized 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 comprehensively 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 aging, in addition to deciphering the regulatory biochemical cascades governing neurodegenerative disease pathogenesis.",
keywords = "aging, hippocampus, neurodegeneration, neuron, non-human primates, proteomics, synapse",
author = "Graham, {Laura C.} and Naldrett, {Michael J.} and Kohama, {Steven G.} and Colin Smith and Lamont, {Douglas J.} and McColl, {Barry W.} and Gillingwater, {Thomas H.} and Paul Skehel and Urbanski, {Henryk F.} and Wishart, {Thomas M.}",
note = "Funding Information: We thank Chris-Anne Mackenzie from the Edinburgh Brain Bank for coordinating the use of human patient tissue and the British consulate in San Francisco for instigating this international collaborative research project. We thank Samantha Eaton and Rachel Kline from the Wishart laboratory for assistance with human sample handling, blotting, and pathway analysis. L.C.G. is supported by a BBSRC studentship and MRC CiC funding. T.M.W. is funded by the BBSRC Institute Strategic Programme (ISPG/5 12-17 and ISPG/1 18-22) and the Euan MacDonald Centre for Motor Neurone Disease Research. S.G.K. and H.F.U. are funded by NIH (OD-011092 and AG-062220). L.C.G. and T.M.W. conceived the study and designed all experiments. L.C.G. performed experiments. S.G.K. and H.F.U. contributed NHP tissues and reagents. C.S. contributed human tissues. M.J.N. and D.J.L. performed mass spectrometry. All authors edited and approved the manuscript. The authors declare no competing interests. Funding Information: We thank Chris-Anne Mackenzie from the Edinburgh Brain Bank for coordinating the use of human patient tissue and the British consulate in San Francisco for instigating this international collaborative research project. We thank Samantha Eaton and Rachel Kline from the Wishart laboratory for assistance with human sample handling, blotting, and pathway analysis. L.C.G. is supported by a BBSRC studentship and MRC CiC funding. T.M.W. is funded by the BBSRC Institute Strategic Programme ( ISPG/5 12-17 and ISPG/1 18-22 ) and the Euan MacDonald Centre for Motor Neurone Disease Research . S.G.K. and H.F.U. are funded by NIH ( OD-011092 and AG-062220 ). Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = apr,
day = "23",
doi = "10.1016/j.celrep.2019.03.096",
language = "English (US)",
volume = "27",
pages = "1018--1026.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}