D2 dopamine receptor A1 allele in Alzheimer disease and aging

Gary W. Small, Ernest P. Noble, Steven S. Matsuyama, Lissy F. Jarvik, Scott Komo, Andrea Kaplan, Terry Ritchie, Meredyth L. Pritchard, Ann M. Saunders, P. Michael Conneally, Allen D. Roses, Jonathan L. Haines, Margaret A Pericak-Vance

Research output: Contribution to journalArticle

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Abstract

Background: The apolipoprotein E4 (APOE*4) allele is a major risk factor for the common forms of late-onset Alzheimer disease (AD), but does not account for all the genetic variation in late-onset AD; hence, other genetic markers must be examined. The D2 dopamine receptor (DRD2) A1 allele is associated with abnormal brain function and decreased DRD2s. These receptors are decreased in hippocampus and amygdala in AD, and allele frequencies may vary with age. Objective: To study APOE and DRD2 genotypes in patients with AD and cognitively intact controls of varying ages. Design: The DRD2 and APOE genotypes were examined in 832 unrelated white subjects, including 554 patterns with AD (486 sporadic; 68 familial) and 278 controls. Logistic regressions tested A1 allele effects on disease status and age, and DRD2 linkage with AD was investigated in 60 families with late-onset AD. Setting: University medical centers. Subjects: Patients (mean ± SD age, 74.6± 8.1 years; range, 52-98 years) had probable AD, according to standard consensus diagnostic criteria; controls (mean± SD age, 69.2 ±8.6 years; range, 50-93 years) were cognitively intact. Main Outcome Measures: Disease status, age, and DRD2 linkage with AD. Results: No association between the DRD2 and APOE alleles was found, and the presence of the A1 allele did not increase the risk for AD. There was also no evidence of linkage between DRD2 and AD. Age analyses, including both patients and controls, indicated a decrease in A1 allele frequency with age. Conclusions: The A1 allele does not contribute to AD risk, alone or in combination with the APOE*4 allele. The DRD2 A1 allele frequencies decrease with age in both patients and controls. Thus, studies of DRD2 disease association need to control for age.

Original languageEnglish
Pages (from-to)281-285
Number of pages5
JournalArchives of Neurology
Volume54
Issue number3
StatePublished - Jan 1 1997
Externally publishedYes

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Dopamine D2 Receptors
Alzheimer Disease
Alleles
Gene Frequency
Apolipoprotein E4
Allele
Alzheimer's Disease
Dopamine
Genotype
Amygdala
Genetic Markers
Hippocampus
Consensus
Logistic Models
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Small, G. W., Noble, E. P., Matsuyama, S. S., Jarvik, L. F., Komo, S., Kaplan, A., ... Pericak-Vance, M. A. (1997). D2 dopamine receptor A1 allele in Alzheimer disease and aging. Archives of Neurology, 54(3), 281-285.

D2 dopamine receptor A1 allele in Alzheimer disease and aging. / Small, Gary W.; Noble, Ernest P.; Matsuyama, Steven S.; Jarvik, Lissy F.; Komo, Scott; Kaplan, Andrea; Ritchie, Terry; Pritchard, Meredyth L.; Saunders, Ann M.; Michael Conneally, P.; Roses, Allen D.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

In: Archives of Neurology, Vol. 54, No. 3, 01.01.1997, p. 281-285.

Research output: Contribution to journalArticle

Small, GW, Noble, EP, Matsuyama, SS, Jarvik, LF, Komo, S, Kaplan, A, Ritchie, T, Pritchard, ML, Saunders, AM, Michael Conneally, P, Roses, AD, Haines, JL & Pericak-Vance, MA 1997, 'D2 dopamine receptor A1 allele in Alzheimer disease and aging', Archives of Neurology, vol. 54, no. 3, pp. 281-285.
Small GW, Noble EP, Matsuyama SS, Jarvik LF, Komo S, Kaplan A et al. D2 dopamine receptor A1 allele in Alzheimer disease and aging. Archives of Neurology. 1997 Jan 1;54(3):281-285.
Small, Gary W. ; Noble, Ernest P. ; Matsuyama, Steven S. ; Jarvik, Lissy F. ; Komo, Scott ; Kaplan, Andrea ; Ritchie, Terry ; Pritchard, Meredyth L. ; Saunders, Ann M. ; Michael Conneally, P. ; Roses, Allen D. ; Haines, Jonathan L. ; Pericak-Vance, Margaret A. / D2 dopamine receptor A1 allele in Alzheimer disease and aging. In: Archives of Neurology. 1997 ; Vol. 54, No. 3. pp. 281-285.
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abstract = "Background: The apolipoprotein E4 (APOE*4) allele is a major risk factor for the common forms of late-onset Alzheimer disease (AD), but does not account for all the genetic variation in late-onset AD; hence, other genetic markers must be examined. The D2 dopamine receptor (DRD2) A1 allele is associated with abnormal brain function and decreased DRD2s. These receptors are decreased in hippocampus and amygdala in AD, and allele frequencies may vary with age. Objective: To study APOE and DRD2 genotypes in patients with AD and cognitively intact controls of varying ages. Design: The DRD2 and APOE genotypes were examined in 832 unrelated white subjects, including 554 patterns with AD (486 sporadic; 68 familial) and 278 controls. Logistic regressions tested A1 allele effects on disease status and age, and DRD2 linkage with AD was investigated in 60 families with late-onset AD. Setting: University medical centers. Subjects: Patients (mean ± SD age, 74.6± 8.1 years; range, 52-98 years) had probable AD, according to standard consensus diagnostic criteria; controls (mean± SD age, 69.2 ±8.6 years; range, 50-93 years) were cognitively intact. Main Outcome Measures: Disease status, age, and DRD2 linkage with AD. Results: No association between the DRD2 and APOE alleles was found, and the presence of the A1 allele did not increase the risk for AD. There was also no evidence of linkage between DRD2 and AD. Age analyses, including both patients and controls, indicated a decrease in A1 allele frequency with age. Conclusions: The A1 allele does not contribute to AD risk, alone or in combination with the APOE*4 allele. The DRD2 A1 allele frequencies decrease with age in both patients and controls. Thus, studies of DRD2 disease association need to control for age.",
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T1 - D2 dopamine receptor A1 allele in Alzheimer disease and aging

AU - Small, Gary W.

AU - Noble, Ernest P.

AU - Matsuyama, Steven S.

AU - Jarvik, Lissy F.

AU - Komo, Scott

AU - Kaplan, Andrea

AU - Ritchie, Terry

AU - Pritchard, Meredyth L.

AU - Saunders, Ann M.

AU - Michael Conneally, P.

AU - Roses, Allen D.

AU - Haines, Jonathan L.

AU - Pericak-Vance, Margaret A

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N2 - Background: The apolipoprotein E4 (APOE*4) allele is a major risk factor for the common forms of late-onset Alzheimer disease (AD), but does not account for all the genetic variation in late-onset AD; hence, other genetic markers must be examined. The D2 dopamine receptor (DRD2) A1 allele is associated with abnormal brain function and decreased DRD2s. These receptors are decreased in hippocampus and amygdala in AD, and allele frequencies may vary with age. Objective: To study APOE and DRD2 genotypes in patients with AD and cognitively intact controls of varying ages. Design: The DRD2 and APOE genotypes were examined in 832 unrelated white subjects, including 554 patterns with AD (486 sporadic; 68 familial) and 278 controls. Logistic regressions tested A1 allele effects on disease status and age, and DRD2 linkage with AD was investigated in 60 families with late-onset AD. Setting: University medical centers. Subjects: Patients (mean ± SD age, 74.6± 8.1 years; range, 52-98 years) had probable AD, according to standard consensus diagnostic criteria; controls (mean± SD age, 69.2 ±8.6 years; range, 50-93 years) were cognitively intact. Main Outcome Measures: Disease status, age, and DRD2 linkage with AD. Results: No association between the DRD2 and APOE alleles was found, and the presence of the A1 allele did not increase the risk for AD. There was also no evidence of linkage between DRD2 and AD. Age analyses, including both patients and controls, indicated a decrease in A1 allele frequency with age. Conclusions: The A1 allele does not contribute to AD risk, alone or in combination with the APOE*4 allele. The DRD2 A1 allele frequencies decrease with age in both patients and controls. Thus, studies of DRD2 disease association need to control for age.

AB - Background: The apolipoprotein E4 (APOE*4) allele is a major risk factor for the common forms of late-onset Alzheimer disease (AD), but does not account for all the genetic variation in late-onset AD; hence, other genetic markers must be examined. The D2 dopamine receptor (DRD2) A1 allele is associated with abnormal brain function and decreased DRD2s. These receptors are decreased in hippocampus and amygdala in AD, and allele frequencies may vary with age. Objective: To study APOE and DRD2 genotypes in patients with AD and cognitively intact controls of varying ages. Design: The DRD2 and APOE genotypes were examined in 832 unrelated white subjects, including 554 patterns with AD (486 sporadic; 68 familial) and 278 controls. Logistic regressions tested A1 allele effects on disease status and age, and DRD2 linkage with AD was investigated in 60 families with late-onset AD. Setting: University medical centers. Subjects: Patients (mean ± SD age, 74.6± 8.1 years; range, 52-98 years) had probable AD, according to standard consensus diagnostic criteria; controls (mean± SD age, 69.2 ±8.6 years; range, 50-93 years) were cognitively intact. Main Outcome Measures: Disease status, age, and DRD2 linkage with AD. Results: No association between the DRD2 and APOE alleles was found, and the presence of the A1 allele did not increase the risk for AD. There was also no evidence of linkage between DRD2 and AD. Age analyses, including both patients and controls, indicated a decrease in A1 allele frequency with age. Conclusions: The A1 allele does not contribute to AD risk, alone or in combination with the APOE*4 allele. The DRD2 A1 allele frequencies decrease with age in both patients and controls. Thus, studies of DRD2 disease association need to control for age.

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