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Clinical and neurobiological correlates of D10S1423 genotype in Alzheimer's disease.
Biol Psychiatry. 1999 Sep 15; 46(6):740-9.BP

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.

Authors+Show Affiliations

Department of Psychiatry, School of Medicine, University of Pittsburgh, Pennsylvania, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10494441

Citation

Zubenko, G S., et al. "Clinical and Neurobiological Correlates of D10S1423 Genotype in Alzheimer's Disease." Biological Psychiatry, vol. 46, no. 6, 1999, pp. 740-9.
Zubenko GS, Hughes HB, Stiffler JS. Clinical and neurobiological correlates of D10S1423 genotype in Alzheimer's disease. Biol Psychiatry. 1999;46(6):740-9.
Zubenko, G. S., Hughes, H. B., & Stiffler, J. S. (1999). Clinical and neurobiological correlates of D10S1423 genotype in Alzheimer's disease. Biological Psychiatry, 46(6), 740-9.
Zubenko GS, Hughes HB, Stiffler JS. Clinical and Neurobiological Correlates of D10S1423 Genotype in Alzheimer's Disease. Biol Psychiatry. 1999 Sep 15;46(6):740-9. PubMed PMID: 10494441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and neurobiological correlates of D10S1423 genotype in Alzheimer's disease. AU - Zubenko,G S, AU - Hughes,H B,3rd AU - Stiffler,J S, PY - 1999/9/24/pubmed PY - 2001/3/28/medline PY - 1999/9/24/entrez SP - 740 EP - 9 JF - Biological psychiatry JO - Biol. Psychiatry VL - 46 IS - 6 N2 - 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. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/10494441/Clinical_and_neurobiological_correlates_of_D10S1423_genotype_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(99)00021-9 DB - PRIME DP - Unbound Medicine ER -