title: Brain pathologies in extreme old age.
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.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Janna H
authors.initials: JH
authors.lastname: Neltner
authors.affiliation: Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Department of Epidemiology, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Ela
authors.initials: E
authors.lastname: Patel
authors.affiliation: Institute of Gerontology, The University of Georgia, Athens, GA, USA.
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Poon
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA, USA.
authors.forename: Gearing
authors.initials: G
authors.lastname: Marla
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
authors.affiliation: Department of Epidemiology and Biostatistics, Temple University, Philadelphia, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Davey
authors.affiliation: Institute of Gerontology, The University of Georgia, Athens, GA, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Johnson
authors.affiliation: Department of Medicine, Tulane Center for Aging, Tulane University, New Orleans, LA, USA.
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
authors.affiliation: Department of Medicine, Tulane Center for Aging, Tulane University, New Orleans, LA, USA.
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pathology, Baptist Health Care, Lexington, KY, USA.
authors.forename: Daron
authors.initials: D
authors.lastname: Davis
authors.affiliation: Department of Psychology, Wayne State University, Detroit MI, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Woodard
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Statistics, University of Kentucky, Lexington, KY, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.affiliation: 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.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology*; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008297:Male; D056892:Mediator Complex; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C492159:MED23 protein, human; D056892:Mediator Complex; C000598624:TARDBP protein, human
keywords: Arteriosclerosis; KATP; Lipohyalinosis; NFT; Neuropathology; Oldest-old; PART; SUR2; Stroke; Synucleinopathy; TDP-43; VCID