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Related Experiment Video

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Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans
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Brain pathologies in extreme old age.

Janna H Neltner1, Erin L Abner2, Gregory A Jicha3

  • 1Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.

Neurobiology of Aging
|November 25, 2015
PubMed
Summary
This summary is machine-generated.

Neuropathology in centenarians reveals that Alzheimer's disease is not universal, but tau pathology is common. A novel ABCC9 gene variant is linked to arteriolosclerosis and hippocampal sclerosis of aging.

Keywords:
ArteriosclerosisKATPLipohyalinosisNFTNeuropathologyOldest-oldPARTSUR2StrokeSynucleinopathyTDP-43VCID

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Area of Science:

  • Neuropathology
  • Gerontology
  • Genetics

Background:

  • Understanding brain changes in extreme old age is crucial for aging research.
  • Centenarian studies offer unique insights into resilience and pathology at the end of the human lifespan.

Purpose of the Study:

  • To investigate the neuropathologic landscape in centenarians.
  • To identify common pathologies and potential genetic risk factors in the very old.

Main Methods:

  • Analysis of neuropathologic data from centenarian cohorts (Georgia Centenarian Study, Nun Study, University of Kentucky Alzheimer's Disease Center).
  • Evaluation of Alzheimer's disease, frontotemporal lobar degeneration, tauopathy, Lewy body pathology, and hippocampal sclerosis of aging.
  • Assessment of arteriolosclerosis, pigment-laden macrophages, and Virchow-Robin spaces.
  • Genetic analysis including the ABCC9 gene variant.

Main Results:

  • Alzheimer's disease pathology (amyloid plaques) was present in 62% of cases; frontotemporal lobar degeneration was absent.
  • Hippocampal neurofibrillary tangles (primary age-related tauopathy) were found in all subjects.
  • Lewy body pathology (16.9%) and hippocampal sclerosis of aging (20.8%) were observed.
  • Moderate to severe arteriolosclerosis was associated with hippocampal sclerosis of aging and the ABCC9 gene variant.

Conclusions:

  • Cerebral multimorbidity is complex in centenarians, with tau pathology being nearly universal.
  • The ABCC9 gene variant represents a novel genetic risk factor for age-related cerebrovascular changes.