Warren A C, Robakis N K, Ramakrishna N, Koo E H, Ross C A, Robb A S, Folstein M F, Price D L, Antonarakis S E
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Genomics. 1987 Dec;1(4):307-12. doi: 10.1016/0888-7543(87)90029-2.
Recently, it has been suggested that Alzheimer's disease is associated with a duplication of the amyloid precursor protein gene localized to chromosome 21q21. In this study, a cloned DNA probe (B2.3), complementary to the sequence coding the beta-amyloid peptide, and DNA polymorphisms adjacent to this sequence were used to determine the number of copies of the beta-amyloid gene in DNA isolated from human blood and brain. Individuals with trisomy 21 (Down syndrome) who were heterozygous for the polymorphisms showed a gene-dosage effect, with one allele exhibiting twice the autoradiographic intensity as the other. Heterozygous individuals with Alzheimer's disease and controls showed equal intensities of the two allelic bands, suggesting that there are only two copies of the beta-amyloid gene in these individuals. In individuals with Alzheimer's disease and in controls who were homozygous for these polymorphisms, the number of copies of the beta-amyloid gene was determined by comparing the autoradiographic intensity of beta-amyloid alleles to that of DNA fragments detected by a reference probe. No difference was detected between these two groups.
