Lewy body pathology is a frequent co-pathology in familial Alzheimer's disease
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Our institution is currently engaged in ongoing genetic studies of familial Alzheimer's disease (AD), which include clinical ascertainment and brain autopsy of both affected and non-affected family members. Here we describe the analysis of 22 AD families, each with at least one family member with a postmortem diagnosis of dementia with Lewy bodies (DLB). For this study, 47 brains were examined according to NINCDS-Reagan Institute criteria for the diagnosis of AD. Lewy body pathology was evaluated with α-synuclein immunohistochemistry. Four families, with either one or two autopsies showing Lewy body pathology, demonstrated linkage to 12p. Five families had two or more autopsies with Lewy body pathology, but their linkage status was unknown. The remaining 13 families had one autopsy demonstrating Lewy bodies. These findings suggest that at least one pathological form of DLB may be familial. In some families, the pathological phenotype is identical in all examined affected family members; but in others, there may be several pathologies that coexist. Careful neuropathological examination of affected family members may prove critical for future genetic analysis of AD and DLB.
KeywordsAlzheimer's disease Dementia with Lewy bodies Autopsy Genetics
The authors gratefully acknowledge the assistance of Autopsy Nurse Coordinators, Mari Szymanski RN, C. and Nancy Sinclaire RN, C. now deceased. We also wish to thank Anne Latham for careful assistance with manuscript preparation. Supported by NIA AG05128; AG19757 and NINDS N39764, Glaxo SmithKline and numerous donations from families to the Joseph and Kathleen Price Bryan Alzheimer's Disease Research Center.
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