Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging

Laura C. Graham, Michael J. Naldrett, Steven G. Kohama, Colin Smith, Douglas J. Lamont, Barry W. McColl, Thomas H. Gillingwater, Paul Skehel, Henryk F. Urbanski, Thomas M. Wishart (Lead / Corresponding author)

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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.

Original languageEnglish
Pages (from-to)1018-1026.e4
Number of pages14
JournalCell Reports
Volume27
Issue number4
Early online date23 Apr 2019
DOIs
Publication statusPublished - 23 Apr 2019

Keywords

  • aging
  • hippocampus
  • neurodegeneration
  • neuron
  • non-human primates
  • proteomics
  • synapse

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    Graham, L. C., Naldrett, M. J., Kohama, S. G., Smith, C., Lamont, D. J., McColl, B. W., Gillingwater, T. H., Skehel, P., Urbanski, H. F., & Wishart, T. M. (2019). Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging. Cell Reports, 27(4), 1018-1026.e4. https://doi.org/10.1016/j.celrep.2019.03.096