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Linkage of an Alzheimer disease susceptibility locus to markers on human chromosome 21.

We assessed linkage between Alzheimer disease (AD) and restriction fragment length polymorphisms (RFLPs) from human chromosome 21 in 8 families selected because of multiple occurrences of AD and large size. Sib-pair analysis demonstrated significant evidence for linkage between 2 markers (D21S1 and D21S11) and disease. Two markers, D21S13 and D21S52, did not yield evidence in favor of linkage to disease and a 5th, D21S16, was uninformative. The results confirm that a susceptibility locus for Alzheimer disease is located on chromosome 21. In contrast to other investigators who demonstrated linkage between AD and chromosome 21 loci, we found evidence in favor of linkage in both late- (greater than age 65) and early-onset families.