Postsynaptic Proteome of Non-Demented Individuals with Alzheimer's Disease Neuropathology

Olga Zolochevska, Nicole Bjorklund, Randall Woltjer, John E. Wiktorowicz, Giulio Taglialatela

    Research output: Contribution to journalArticlepeer-review

    21 Scopus citations

    Abstract

    Some individuals, here referred to as Non-Demented with Alzheimer's Neuropathology (NDAN), retain their cognitive function despite the presence of amyloid plaques and tau tangles typical of symptomatic Alzheimer's disease (AD). In NDAN, unlike AD, toxic amyloid-β oligomers do not localize to the postsynaptic densities (PSDs). Synaptic resistance to amyloid-β in NDAN may thus enable these individuals to remain cognitively intact despite the AD-like pathology. The mechanism(s) responsible for this resistance remains unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. The present study uses a proteomic approach to compare the hippocampal postsynaptic densities of NDAN, AD, and healthy age-matched persons to identify protein signatures characteristic for these groups. Subcellular fractionation followed by 2D gel electrophoresis and mass spectrometry were used to analyze the PSDs. We describe fifteen proteins which comprise the unique proteomic signature of NDAN PSDs, thus setting them apart from control subjects and AD patients.

    Original languageEnglish (US)
    Pages (from-to)659-682
    Number of pages24
    JournalJournal of Alzheimer's disease : JAD
    Volume65
    Issue number2
    DOIs
    StatePublished - 2018

    Keywords

    • Alzheimer’s disease
    • non-demented with AD-like pathology
    • postsynaptic density proteome
    • synapse

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Clinical Psychology
    • Geriatrics and Gerontology
    • Psychiatry and Mental health

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