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 alpha-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.
Trembath
Yuri
Y
Department of Pathology, Section of Neuropathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA.
Rosenberg
Carolyn
C
Ervin
John F
JF
Schmechel
Donald E
DE
Gaskell
Perry
P
Pericak-Vance
Margaret
M
Vance
Jeffery
J
Hulette
Christine M
CM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D001344:Autopsy / Q000379:methods; D002881:Chromosomes, Human, Pair 12; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein