Article type: Research Article
Authors: Tsuang, Debby W.a; b; g; * | Riekse, Robert G.d | Purganan, Kristina M.a; g | David, Andrew C.a; g | Montine, Thomas J.f | Schellenberg, Gerard D.b; d | Steinbart, Ellen J.b; e | Petrie, Eric C.a; g | Bird, Thomas D.b; e | Leverenz, James B.a; c; e; g
Affiliations: [a] Mental Illness Research, Education, and Clinical Centers, Veteran Affairs Puget Sound Health Care System, Seattle, WA, 98108, USA | [b] Geriatric Research, Education, and Clinical Centers, Veteran Affairs Puget Sound Health Care System, Seattle, WA, 98108, USA | [c] Parkinson's Disease Research, Education, and Clinical Centers, Veteran Affairs Puget Sound Health Care System, Seattle, WA, 98108, USA | [d] Department of Medicine (Gerontology/Geriatrics), Neurology, University of Washington School of Medicine, Seattle, WA, 98195, USA | [e] Department of Neurology, University of Washington School of Medicine, Seattle, WA, 98195, USA | [f] Department of Pathology (Neuropathology), University of Washington School of Medicine, Seattle, WA, 98195, USA | [g] Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA
Correspondence:
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Corresponding author: Debby W. Tsuang, M.D., VA Puget Sound Health Care System (S116), 1660 South Columbian Way, Seattle, WA, 98108, USA. Tel.: +1 206 277 1333; Fax: +1 206 277 4731; E-mail: dwt1@u.washington.edu.
Abstract: Background: Lewy body pathology (LBP) is a common finding in Alzheimer's disease (AD), but the pathophysiology for this coexistent pathology remains unclear. Methods: We ascertained late-onset dementia (mean age > 60 years old) families with at least 3 autopsies. We then conducted systematic alpha-synuclein (SNCA) immunostaining to determine the frequency and distribution of LBP in families with late-onset AD. Results: All 32 subjects met NIA-Reagan neuropathological criteria for “high likelihood” of having AD. Hematoxylin and eosin staining detected LBP in the substantia nigra (SN) in 8 (25%) individuals. SNCA immunostaining detected LBP in 21 individuals (66%). While all subjects with SN LBP had co-existent amygdala LBP, many (9/21, 43%) of the cases with amygdala LBP did not have coexistent SN LBP (McNemar's chi-square test, p=0.008). Each family had at least two cases with LBP, but no family had LBP in all autopsied cases. Conclusions: Presence of significant AD pathology in one family member was highly predictive of similar pathology in other family members. However, despite the use of more sensitive SNCA immunohistochemistry, the presence of LBP was variable within all 7 families. Consistent with previous studies in sporadic and familial AD, the amygdala appeared to be the most vulnerable region for LBP in AD. Additional clinical, neuropathologic, and genetic studies are necessary to determine the clinical and pathological significance of LBP in AD.
Keywords: Lewy body, alpha-synuclein, Alzheimer's disease, amygdala
DOI: 10.3233/JAD-2006-9302
Journal: Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 235-242, 2006
