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Neurobiol Aging. 2016 Jan;37:1-11. doi: 10.1016/j.neurobiolaging.2015.10.009. Epub 2015 Oct 19.

Brain pathologies in extreme old age.

Author information

1
Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
2
Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
3
Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky, Lexington, KY, USA.
4
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
5
Institute of Gerontology, The University of Georgia, Athens, GA, USA.
6
Department of Pathology, Emory University, Atlanta, GA, USA.
7
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
8
Department of Epidemiology and Biostatistics, Temple University, Philadelphia, PA, USA.
9
Department of Medicine, Tulane Center for Aging, Tulane University, New Orleans, LA, USA.
10
Department of Pathology, Baptist Health Care, Lexington, KY, USA.
11
Department of Psychology, Wayne State University, Detroit MI, USA.
12
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Statistics, University of Kentucky, Lexington, KY, USA.
13
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
14
Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. Electronic address: pnels2@email.uky.edu.

Abstract

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.

KEYWORDS:

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

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