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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)
OBJECTIVES It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-epsilon4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. SUBJECTS A total of 2,233 probands who met criteria for probable or definite AD and their 14,668(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)
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)
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)
Tumor necrosis factor (TNF) is an important proinflammatory cytokine that is upregulated in Alzheimer disease (AD) patients and involved with AD genes. Several TNF promoter polymorphisms that increase expression are associated with inflammatory and infectious diseases. We previously reported results that detected a AD associated region near the TNF gene.(More)
Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of psychosis, 30-60% of the time. Positive symptoms of psychosis have been shown to appear prior to the onset of dementia to be accompanied by greater cognitive deficits, and to predict a more rapid decline. A study of the distribution of AD with psychosis (ADP) in families from(More)
Other than the APOE peak at 19q13, the 9q22 region was identified in our original genomic scan as the candidate region with the highest multipoint lod score (MLS) in the subset of late onset Alzheimer's Disease (AD) families (MLS = 2.9 at 101 cM) from the NIMH Genetics Initiative sample. We have now genotyped an additional 12 short tandem repeats (STR) in(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)
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)