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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(More)
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(More)
Mutations in the tau gene have been described in families affected by frontotemporal dementia with parkinsonism linked to chromosome 17. The authors performed a genetic and biochemical analysis of this gene and its product in the parkinsonism dementia complex of Guam, a disorder characterized by the extensive formation of neurofibrillary tangles. The tau(More)
An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We(More)
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(More)
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. Northern and Western analyses and in situ(More)
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