Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.

The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n=945).

Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease.

Genome-wide linkage studies have defined a broad susceptibility region for late-onset Alzheimer's disease on chromosome 12, which contains the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt signaling. Here, we report the association between common LRP6 variants and late-onset Alzheimer's disease in a multicenter case-control series as well as in a large family-based series ascertained by the National Institute of Mental Health-National Institute on Aging Genetics Initiative. As shown in the genome-wide linkage studies, our association depends mainly on apolipoprotein E-epsilon4 (APOE-epsilon4) carrier status.

The dardarin G 2019 S mutation is a common cause of Parkinson's disease but not other neurodegenerative diseases.

Mutations in the leucine-rich kinase 2 gene (LRRK 2) encoding dardarin, on chromosome 12, are a common cause of familial and sporadic Parkinson's disease. The most common mutation, a heterozygous 6055 G>A transition (G 2019 S) accounts for approximately 3--10% of familial Parkinson's disease and 1--8% sporadic Parkinson's disease in several European-derived populations. Some families with disease caused by LRRK 2 mutations have been reported to include patients with highly variable clinical and pathological features.

Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease.

We performed an affected sib-pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late-onset Alzheimer's disease (AD) in a sample comprising 428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57).

Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.

The frequency and relative contribution of DJ-1 mutations in early-onset Parkinson's disease (EOPD) is currently unknown. We analyzed a cohort of 89 EOPD patients (mean age at onset of PD +/- SD, 41.5 +/- 7.