Lewy body pathology is a frequent co-pathology in familial Alzheimer's disease
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
- 4.Hashimoto M, Hsu LJ, Rockenstein E, Takenouchi T, Mallory M, Masliah E (2002) α-Synuclein protects against oxidative stress via inactivation of the C-jun N-terminal kinase stress signaling pathway in neuronal cells. J Biol Chem 14:14Google Scholar
- 8.Hyman BT, Trojanowski JQ (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097PubMedGoogle Scholar
- 12.Kehoe P, Wavrant-De Vrieze F, Crook R, et al (1999) A full genome scan for late onset Alzheimer's disease. Hum Mol Genet 8:237–245Google Scholar
- 20.Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farer M, Wolozin B (2000) The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J Neurosci 20:6048–6054Google Scholar
- 27.Scott WK, Grubber JM, Conneally PM, et al (2000) Fine mapping of the chromosome 12 late-onset Alzheimer disease locus: potential genetic and phenotypic heterogeneity. Am J Hum Genet 66:922–932Google Scholar