ISSN:
1432-0533
Keywords:
Key words Amyloid precursor protein gene
;
Archival
;
neuropathological tissue
;
Mitochondrial NADH
;
dehydrogenase subunit gene ND2
;
Polymerase chain
;
reaction-based genomic sequencing
;
Quantitative
;
immunocytochemical analysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Molecular genetic analysis was performed in two autopsy-confirmed cases of early-onset Alzheimer's disease belonging to a large German pedigree [FAD2, according to the nomenclature of St. George-Hyslop, et al. (1987) Science 235 : 885–890]. The disease in this family has been linked to chromosome 14. As gene interactions are considered to influence the age of onset and tissue pathology in Alzheimer's disease, we have studied three candidate genes that could modify disease progression. In this study a new polymerase chain reaction (PCR) assay was established for apolipoprotein E genotyping in archival neuropathological tissue, exon 17 of the amyloid precursor protein gene was directly sequenced, and a candidate mutation site at nucleotide (nt) 5460 of the mitochondrial NADH dehydrogenase subunit gene ND2 was analyzed employing PCR followed by HphI digestion. Whereas no sequence variations were detected in exon 17APP or at nt5460 of mitochondrial DNA, the apolipoprotein E genotypes of the two cases differed. Neuropathological examination revealed a higher number of βA4-positive amyloid plaques and a larger total tissue area covered by βA4 deposits in the ε3/ε3 homozygote. In contrast, the number of cortical neurofibrillary tangles and the number of plaques with tau-positive neurites appeared to be higher in the ε3/ε4 heterozygote. Our findings support the view that the chromosome 14 genetic defect, rather than apolipoprotein E genotype, is the preeminent factor determining Alzheimer's disease pathology in this family.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00296509
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