Clinical and neurobiological correlates of D10S1423 genotype in Alzheimer's disease

Background: In a previous genome survey, we detected associations of allele s at six microsatellite loci with typical-onset AD, including the 234bp all ele of the D10S1423 locus. The goal of the current study was to explore the clinical, neuropathalogical, and neurochemical correlates of the D10S1423 234bp allele in a group of 50 autopsy-confirmed cases of Alzheimer's diseas e (AD) who lacked other brain diseases. Methods: Clinical assessments were performed as part of a longitudinal stud y of AD and related disorders. Autopsies were performed using standardized methods and diagnoses were made according to established criteria. Genotypi ng, morphometry, and neurochemical analyses were performed using postmortem brain tissue. Results: Patients with AD who carried the D10S1423 234bp allele manifested substantial reductions in dopamine levels in all six cortical regions exami ned. In contrast carriers tended to have higher concentrations of cortical norepinephrine and revealed a dosage effect of the D10S1423 234bp allele. Conclusions: These findings support the results of our genome survey and su ggest that a novel susceptibility gene far AD resides near the D10S1423 loc us. The characterization of biologically meaningful subtypes, including gen otypic subtypes with particular neurobiological derangements, may be import ant for the advancement of experimental therapeutics in AD. (C) 1999 Societ y of Biological Psychiatry.