Brain pathologies in extreme old age

• Type of Material: Article
• Authors: Janna H. Neltner, University of Kentucky; Erin L. Abner, University of Kentucky; Gregory A. Jicha, University of Kentucky; Frederick A. Schmitt, University of Kentucky; Ela Patel, University of Kentucky; Leonard W. Poon, The University of Georgia; Marla Gearing, Emory University; Robert C. Green, Brigham and Women’s Hospital and Harvard Medical School; Adam Davey, Temple University; Mary Ann Johnson, The University of Georgia; S. Michael Jazwinski, Tulane University; Sangkyu Kim, Tulane University; Daron Davis, Baptist Health Care; John L. Woodard, Wayne State University; Richard J. Kryscio, University of Kentucky; Linda J. Van Eldik, University of Kentucky; Peter T. Nelson, University of Kentucky
• Language: English
• Date: 2016-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neurobiolaging.2015.10.009
• Title of Journal or Parent Work: Neurobiology of Aging
• ISSN: 0197-4580
• Volume: 37
• Start Page: 1
• End Page: 11
• Grant/Funding Information: This study was supported by NIH grants R01 NS061933, R01 AG19241, P01 AG17553, P30 AG028383, and U01 AG016976.
• Keywords: pathology; Alzheimer's disease; old age; Cerebrovascular disease; medicine

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 University of Kentucky (UK-ADC), incorporating data from the Georgia Centenarian Study (N=49 cases included), the Nun Study (N=17), and UK-ADC (N=11) cohorts. Average age of death was 102.0 years (range: 98–107) overall. Alzheimer’s disease (AD) pathology was not universal (62% with “moderate” or “frequent” neuritic amyloid plaque densities) whereas frontotemporal lobar degeneration (FTLD) was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy [PART]) were observed in every case. Lewy body pathology was seen in 16.9% of subjects, hippocampal sclerosis of aging (HS-Aging) in 20.8%. We describe anatomical 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 HS-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.