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Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Abeta, the principal component of beta-amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the IDE gene, in 435(More)
Alpha-2-macroglobulin (alpha-2M; encoded by the gene A2M) is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits. Analysis of a deletion in the A2M gene at the 5' splice site of 'exon II' of the bait region(More)
Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent(More)
OBJECTIVES To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites. DESIGN We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population. SUBJECTS Five(More)
OBJECTIVE To explore the impact of apoE-4 on Alzheimer's disease (AD) and its age at onset. DESIGN A genetic linkage study using affected relative pairs, predominantly siblings. SETTING Three academic medical centers ascertained subjects from memory disorder clinics, nursing homes, and the local community. SUBJECTS 310 families including 679 subjects(More)
IMPORTANCE Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic(More)
High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with(More)
Substantial laboratory evidence suggests Transforming Growth Factor-beta1 (TGFB1) is linked to Alzheimer's Disease (AD) pathology. The purpose of the study was to estimate the genetic association of TGFB1 with AD while controlling for apolipoprotein E4 allele (APOE4) status, the only well-established genetic risk factor for AD. Two study populations were(More)
BACKGROUND The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity. STUDY DESIGN Cross-sectional. SETTING & PARTICIPANTS 23,405 participants (mean age, 64.9 +/- 9.6 years) with baseline measurements of creatinine and cognitive function participating in(More)
BACKGROUND Depression symptoms may be associated with the development of Alzheimer disease (AD). OBJECTIVES To evaluate the association between depression symptoms and risk of AD, and to explore the temporal aspects of this association. SETTING Academic institutions with specialized memory clinics. DESIGN Cross-sectional, family-based, case-control(More)