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Open AccessGenetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center
The Knight-Alzheimer Disease Research Center (Knight-ADRC) at Washington University in St. Louis has pioneered and led worldwide seminal studies that have expanded our clinical, social, pathological, and molec...
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Article
Open AccessTOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma
Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specif...
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Article
Open AccessOrgan aging signatures in the plasma proteome track health and disease
Animal studies show aging varies between individuals as well as between organs within an individual1–4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of ...
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Article
Open AccessIntegrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP
Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive...
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Article
Sex-specific genetic predictors of Alzheimer’s disease biomarkers
Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer’s disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences...
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Open AccessGenetic variants associated with Alzheimer’s disease confer different cerebral cortex cell-type population structure
Alzheimer’s disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the specific effects that pathological mutations and coding variants associated with AD have on the ...
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Article
Open AccessParkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels
The genetic architecture of Parkinson’s Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the ex...
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Article
A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease
The authors identified a protective genetic allele associated with lower PU.1 (SPI1) expression in myeloid cells by conducting a genome-wide scan of Alzheimer's disease (AD). PU.1 binds the promoters of AD-associ...
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Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers
More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information...
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Open AccessChitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40
Alzheimer’s disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ42 ratio is...
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Article
Open AccessGenetic studies of plasma analytes identify novel potential biomarkers for several complex traits
Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins t...
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Open AccessRole of ABCA7 loss-of-function variant in Alzheimer's disease: a replication study in European–Americans
A recent study found a significant increase of ABCA7 loss-of-function variants in Alzheimer’s disease (AD) cases compared to controls. Some variants were located on noncoding regions, but it was demonstrated that...
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Article
Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease
Whole-exome sequencing reveals that a rare variant of phospholipase D3 (PLD3(V232M)) segregates with Alzheimer’s disease status in two independent families and doubles risk for the disease in case–control series,...
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A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks
Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol depen...
