Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging

Laura C. Graham, Michael J. Naldrett, Steven Kohama, Colin Smith, Douglas J. Lamont, Barry W. McColl, Thomas H. Gillingwater, Paul Skehel, Henryk Urbanski, Thomas M. Wishart

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    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 (US)
    Pages (from-to)1018-1026.e4
    JournalCell Reports
    Volume27
    Issue number4
    DOIs
    StatePublished - Apr 23 2019

    Fingerprint

    Synapses
    Primates
    Brain
    Aging of materials
    Proteome
    Neurodegenerative diseases
    Occipital Lobe
    Dendritic Spines
    Macaca mulatta
    Neurodegenerative Diseases
    Proteomics
    Hippocampus
    Tissue
    Population

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Graham, L. C., Naldrett, M. J., Kohama, S., Smith, C., Lamont, D. J., McColl, B. W., ... 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

    Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging. / Graham, Laura C.; Naldrett, Michael J.; Kohama, Steven; Smith, Colin; Lamont, Douglas J.; McColl, Barry W.; Gillingwater, Thomas H.; Skehel, Paul; Urbanski, Henryk; Wishart, Thomas M.

    In: Cell Reports, Vol. 27, No. 4, 23.04.2019, p. 1018-1026.e4.

    Research output: Contribution to journalArticle

    Graham, LC, Naldrett, MJ, Kohama, S, Smith, C, Lamont, DJ, McColl, BW, Gillingwater, TH, Skehel, P, Urbanski, H & Wishart, TM 2019, 'Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging', Cell Reports, vol. 27, no. 4, pp. 1018-1026.e4. https://doi.org/10.1016/j.celrep.2019.03.096
    Graham LC, Naldrett MJ, Kohama S, Smith C, Lamont DJ, McColl BW et al. Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging. Cell Reports. 2019 Apr 23;27(4):1018-1026.e4. https://doi.org/10.1016/j.celrep.2019.03.096
    Graham, Laura C. ; Naldrett, Michael J. ; Kohama, Steven ; Smith, Colin ; Lamont, Douglas J. ; McColl, Barry W. ; Gillingwater, Thomas H. ; Skehel, Paul ; Urbanski, Henryk ; Wishart, Thomas M. / Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging. In: Cell Reports. 2019 ; Vol. 27, No. 4. pp. 1018-1026.e4.
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