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Variation within genes has important implications for all biological traits. We identified 3899 single nucleotide polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all(More)
CONTEXT Frequent participation in cognitively stimulating activities has been hypothesized to reduce risk of Alzheimer disease (AD), but prospective data regarding an association are lacking. OBJECTIVE To test the hypothesis that frequent participation in cognitive activities is associated with a reduced risk of AD. DESIGN Longitudinal cohort study with(More)
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A(More)
While a potential causal factor in Alzheimer's disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in(More)
CONTEXT The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease. OBJECTIVE To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy. DESIGN, SETTING, AND PARTICIPANTS(More)
The aim of this study was to improve the neuropathologic recognition and provide criteria for the pathological diagnosis in the neurodegenerative diseases grouped as frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent advances in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest Consortium for(More)
BACKGROUND Participation in cognitively stimulating activities is hypothesized to be associated with risk of AD, but knowledge about this association is limited. METHODS A biracial community in Chicago was censused, persons aged 65 years and older were asked to participate in an interview, and 6,158 of 7,826 (79%) eligible persons did so. As part of the(More)
The Memory and Aging Project is a longitudinal, epidemiologic clinical-pathologic cohort study of common chronic conditions of aging with an emphasis on decline in cognitive and motor function and risk of Alzheimer's disease (AD). In this manuscript, we first summarize the study design and methods. Then, we present data on: (1) the relation of motor(More)
OBJECTIVE To examine the relation of National Institute on Aging-Reagan (NIA-Reagan) neuropathologic criteria of Alzheimer disease (AD) to level of cognitive function in persons without dementia or mild cognitive impairment (MCI). METHODS More than 2,000 persons without dementia participating in the Religious Orders Study or the Memory and Aging Project(More)
Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between(More)