Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Abner, Erin L.a | Kryscio, Richard J.a; b | Schmitt, Frederick A.a; c | SantaCruz, Karen S.d | Jicha, Gregory A.a; c | Lin, Yushuna; b | Neltner, Janna M.f | Smith, Charles D.a; c | Van Eldik, Linda J.a; e | Nelson, Peter T.a; f; *
Affiliations: [a] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [b] Department of Statistics, University of Kentucky, Lexington, KY, USA | [c] Department of Neurology, University of Kentucky, Lexington, KY, USA | [d] Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA | [e] Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA | [f] Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA
Correspondence: [*] Correspondence to: Peter T. Nelson, MD PhD, Department of Pathology, Division of Neuropathology and the Sanders-Brown Center on Aging, Rm 311, Sanders-Brown Building, 800 S. Limestone, University of Kentucky, Lexington, KY 40536-0230, USA. Tel.: +1 859 257 1412 x 254; Fax: +1 859 257 6054; E-mail: pnels2@email.uky.edu.
Abstract: Among individuals who were cognitively intact before death, autopsies may reveal some Alzheimer's disease-type pathology. The presence of end-stage pathology in cognitively intact persons would support the hypothesis that pathological markers are epiphenomena. We assessed advanced neurofibrillary (Braak stages V and VI) pathology focusing on nondemented individuals. Data from the National Alzheimer's Coordinating Center database (n = 4,690 included initially) and from the Nun Study (n = 526 included initially) were analyzed, with antemortem information about global cognition and careful postmortem studies available from each case. Global cognition (final Mini-Mental State Examination scores (MMSE) and clinical ‘dementia’ status) was correlated with neuropathology, including the severity of neurofibrillary pathology (Braak stages and neurofibrillary tangle counts in cerebral neocortex). Analyses support three major findings: 1. Braak stage V cases and Braak VI cases are significantly different from each other in terms of associated antemortem cognition; 2. There is an appreciable range of pathology within the category of Braak stage VI based on tangle counts such that brains with the most neurofibrillary tangles in neocortex always had profound antemortem cognitive impairment; and 3. There was no nondemented case with final MMSE score of 30 within a year of life and Braak stage VI pathology. It may be inappropriate to combine Braak stages V and VI cases, particularly in patients with early cognitive dysfunction, since the two pathological stages appear to differ dramatically in terms of both pathological severity and antemortem cognitive status. There is no documented example of truly end-stage neurofibrillary pathology coexisting with intact cognition.
Keywords: GRN, miRNA, microRNA, neurofibrillary tangles, neuropathology
DOI: 10.3233/JAD-2011-101980
Journal: Journal of Alzheimer's Disease, vol. 25, no. 3, pp. 445-453, 2011
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl