Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death.

Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are responsible for autosomal dominant and sporadic Parkinson disease (PD), possibly exerting their effects via a toxic gain of function. A common p.G2019S mutation (rs34637584:A>G) is responsible for up to 30-40% of PD cases in some ethnic populations.

Abeta40 inhibits amyloid deposition in vivo.

Numerous studies have established a pivotal role for Abeta42 in Alzheimer's disease (AD) pathogenesis. In contrast, although Abeta40 is the predominant form of amyloid beta (Abeta) produced and accumulates to a variable degree in the human AD brain, its role in AD pathogenesis has not been established. It has generally been assumed that an increase in Abeta40 would accelerate amyloid plaque formation in vivo.

Abeta42 is essential for parenchymal and vascular amyloid deposition in mice.

Considerable circumstantial evidence suggests that Abeta42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Abeta42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Abeta1-40 or Abeta1-42 in the absence of human amyloid beta protein precursor (APP) overexpression.

Expression of mBRI2 in mice.

Mutations in the BRI(2) gene cause the autosomal dominant neurodegenerative diseases familial British dementia (FBD) and familial Danish dementia (FDD). BRI(2) is a member of a family of type 2 integral transmembrane spanning proteins, including mBRI(2), its murine homologue. The function of BRI(2) is unknown.

Apolipoprotein E4 and tau allele frequencies among Choctaw Indians.

Apolipoprotein genotyping and tau haplotyping were carried out on a series of cases with dementia and controls from the Choctaw Nation of Oklahoma. Both the Apolipoprotein E4 allele frequency and the tau H2 haplotype frequency were low in the Choctaw compared with Caucasians and there was the possibility that the association between dementia and the E4 allele was weaker than in Caucasians.