The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 8100437 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1558-1497 (Electronic) Linking ISSN: 01974580 NLM ISO Abbreviation: Neurobiol Aging Subsets: MEDLINE
    • Publication Information:
      Publication: New York : Elsevier
      Original Publication: Fayetteville, N.Y. : Ankho International.
    • Subject Terms:
      Aging/*pathology ; Aging/*psychology ; Amyloid beta-Peptides/*metabolism ; Blood Vessels/*pathology ; Brain/*metabolism ; Brain/*pathology ; DNA-Binding Proteins/*metabolism ; alpha-Synuclein/*metabolism ; tau Proteins/*metabolism; Aged ; Aged, 80 and over ; Aging/metabolism ; Apolipoprotein E4/metabolism ; Brain/blood supply ; Cognition ; Depression ; Female ; Humans ; Male ; Memory ; Middle Aged ; Organ Size ; Psychomotor Performance
    • Abstract:
      Many individuals live to older ages without clinical impairment. It is unknown whether brain pathologies in these individuals are associated with subtle clinical deficits. We analyzed the brains of 161 clinically normal (Clinical Dementia Rating score = 0) older individuals enrolled in the Mayo Clinic Patient Registry or Study of Aging. We assessed for the presence and burden of beta-amyloid, tau, alpha-synuclein, TDP-43, and vascular pathology. We investigated whether pathologies were associated with antemortem cognitive and motor function, depression, MRI volumetric measures, or the apolipoprotein E (APOE) ε4 allele. Eighty-six percent had at least 1 pathology, and 63% had mixed pathologies. Tau and vascular pathology were associated with poorer memory scores. Tau was also associated with poorer general cognition scores and smaller amygdala, hippocampi, and entorhinal cortex volumes. Beta-amyloid neuritic plaque burden was associated with greater depression scores. The presence of a greater number of pathologies was associated with APOE e4 carrier status and with poorer memory performance. Some dementia-related pathologies are associated with poorer performance in clinical measures and brain atrophy in the unimpaired elderly.
      (Copyright © 2019 Elsevier Inc. All rights reserved.)
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    • Grant Information:
      R01 AG041851 United States AG NIA NIH HHS; P50 AG016574 United States AG NIA NIH HHS; R01 AG037491 United States AG NIA NIH HHS; R37 AG011378 United States AG NIA NIH HHS; U01 AG006786 United States AG NIA NIH HHS
    • Contributed Indexing:
      Keywords: Brain volume; Clinically normal aging; Cognition; Depression; Neurodegenerative pathology; TDP-43; Vascular pathology
    • Accession Number:
      0 (Amyloid beta-Peptides)
      0 (Apolipoprotein E4)
      0 (DNA-Binding Proteins)
      0 (TARDBP protein, human)
      0 (alpha-Synuclein)
      0 (tau Proteins)
    • Publication Date:
      Date Created: 20190219 Date Completed: 20191206 Latest Revision: 20211201
    • Publication Date:
      20231215
    • Accession Number:
      PMC6486870
    • Accession Number:
      10.1016/j.neurobiolaging.2019.01.008
    • Accession Number:
      30776649