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

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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.

Original languageEnglish (US)
Pages (from-to)26-36
Number of pages11
JournalNeurobiology of aging
Volume77
DOIs
StatePublished - May 1 2019

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alpha-Synuclein
Amyloid
Blood Vessels
Pathology
Apolipoprotein E4
Amyloid Plaques
Cognition
Dementia
Brain
Depression
Entorhinal Cortex
Apolipoproteins E
Amygdala
Atrophy
Registries
Hippocampus
Alleles

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

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title = "The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals",
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.",
keywords = "Brain volume, Clinically normal aging, Cognition, Depression, Neurodegenerative pathology, TDP-43, Vascular pathology",
author = "Wennberg, {Alexandra M.} and Whitwell, {Jennifer Lynn} and Nirubol Tosakulwong and Weigand, {Stephen D.} and Murray, {Melissa E} and Machulda, {Mary Margaret} and Leonard Petrucelli and Mielke, {Michelle M} and Jack, {Clifford R Jr.} and Knopman, {David S} and Parisi, {Joseph E} and Petersen, {Ronald Carl} and Dickson, {Dennis W} and Josephs, {Keith Anthony}",
year = "2019",
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doi = "10.1016/j.neurobiolaging.2019.01.008",
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T1 - The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals

AU - Wennberg, Alexandra M.

AU - Whitwell, Jennifer Lynn

AU - Tosakulwong, Nirubol

AU - Weigand, Stephen D.

AU - Murray, Melissa E

AU - Machulda, Mary Margaret

AU - Petrucelli, Leonard

AU - Mielke, Michelle M

AU - Jack, Clifford R Jr.

AU - Knopman, David S

AU - Parisi, Joseph E

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

AU - Josephs, Keith Anthony

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Brain volume

KW - Clinically normal aging

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KW - Depression

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KW - TDP-43

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