Abstract
Background: In a previous genome survey, we detected associations of alleles at six
microsatellite loci with typical-onset AD, including the 234bp allele of the D10S1423
locus. The goal of the current study was to explore the clinical, neuropathological,
and neurochemical correlates of the D10S1423 234bp allele in a group of 50 autopsy-confirmed
cases of Alzheimer’s disease (AD) who lacked other brain diseases.
Methods: Clinical assessments were performed as part of a longitudinal study of AD
and related disorders. Autopsies were performed using standardized methods and diagnoses
were made according to established criteria. Genotyping, 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 examined. 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 suggest that
a novel susceptibility gene for AD resides near the D10S1423 locus. The characterization
of biologically meaningful subtypes, including genotypic subtypes with particular
neurobiological derangements, may be important for the advancement of experimental
therapeutics in AD.
Keywords
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Article info
Publication history
Accepted:
January 19,
1999
Received in revised form:
December 22,
1998
Received:
September 21,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
