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

Alexandra M. Wennberg, Jennifer L. Whitwell, Nirubol Tosakulwong, Stephen D. Weigand, Melissa E. Murray, Mary M. Machulda, Leonard Petrucelli, Michelle M. Mielke, Clifford R. Jack, David S. Knopman, Joseph E. Parisi, Ronald C. Petersen, Dennis W. Dickson, Keith A. Josephs

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)26-36
Number of pages11
JournalNeurobiology of aging
StatePublished - May 2019


  • Brain volume
  • Clinically normal aging
  • Cognition
  • Depression
  • Neurodegenerative pathology
  • TDP-43
  • Vascular pathology

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


Dive into the research topics of 'The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals'. Together they form a unique fingerprint.

Cite this