Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging

TY - JOUR

T1 - Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging

AU - Graham, Laura C.

AU - Naldrett, Michael J.

AU - Kohama, Steven G.

AU - Smith, Colin

AU - Lamont, Douglas J.

AU - McColl, Barry W.

AU - Gillingwater, Thomas H.

AU - Skehel, Paul

AU - Urbanski, Henryk F.

AU - Wishart, Thomas M.

N1 - T.M.W. is funded bythe 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)

PY - 2019/4/23

Y1 - 2019/4/23

N2 - 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.

AB - 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.

KW - aging

KW - hippocampus

KW - neurodegeneration

KW - neuron

KW - non-human primates

KW - proteomics

KW - synapse

UR - https://www.scopus.com/pages/publications/85064464272

U2 - 10.1016/j.celrep.2019.03.096

DO - 10.1016/j.celrep.2019.03.096

M3 - Article

C2 - 31018120

AN - SCOPUS:85064464272

SN - 2211-1247

VL - 27

SP - 1018-1026.e4

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -