Brain pathologies in extreme old age

Janna H. Neltner, Erin L. Abner, Gregory A. Jicha, Frederick A. Schmitt, Ela Patel, Leonard W. Poon, Gearing Marla, Robert C. Green, Adam Davey, Mary Ann Johnson, S. Michal Jazwinski, Sangkyu Kim, Daron Davis, John L. Woodard, Richard J. Kryscio, Linda J. Van Eldik, Peter T. Nelson

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at the University of Kentucky Alzheimer's Disease Center, incorporating data from the Georgia Centenarian Study (n = 49 cases included), Nun Study (n = 17), and University of Kentucky Alzheimer's Disease Center (n = 11) cohorts. Average age of death was 102.0 (range: 98–107) years overall. Alzheimer's disease pathology was not universal (62% with “moderate” or “frequent” neuritic amyloid plaque densities), whereas frontotemporal lobar degeneration was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy) were observed in every case. Lewy body pathology was seen in 16.9% of subjects and hippocampal sclerosis of aging in 20.8%. We describe anatomic distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both hippocampal sclerosis of aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalNeurobiology of Aging
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
We are deeply grateful to all the study volunteers. We thank Sonya Anderson for technical support and Greg Cooper, MD, Nancy Stiles, MD, and Allison Caban-Holt, PhD, for the clinical evaluations. This study was supported by National Institutes of Health grants R01 NS061933 , R01 AG19241 , P01 AG17553 , P30 AG028383 , and U01 AG016976 .

Publisher Copyright:
© 2016 Elsevier Inc.


  • Arteriosclerosis
  • KATP
  • Lipohyalinosis
  • NFT
  • Neuropathology
  • Oldest-old
  • PART
  • SUR2
  • Stroke
  • Synucleinopathy
  • TDP-43
  • VCID

ASJC Scopus subject areas

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


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