Presenilin 1 (PS1) and PS2 are evolutionarily conserved transmembrane proteins of the aspartyl protease family. Initially, they were reported to be associated with the early onset of familial, early-onset Alzheimer's disease. PS1 has been implicated in several crucial brain functions including developmental processes, synaptic plasticity, and processing of various molecules, while PS2 has been ...

Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve learning and memory in several pharmacological models of Alzheimer's disease (AD). In the present study, the effect of memantine on locomotor activity, social behavior, and spatial learning was assessed in a transgenic mouse model of AD. Eight-month-old male C57BL/6J mice car...

Mutations in the presenilin 1 gene (PS1) account for the majority of early onset, familial, autosomal dominant forms of Alzheimer’s disease (AD), whereas its role in other late onset forms of AD remains unclear. A −48 C/T polymorphism in the PS1 promoter has been associated with an increased genetic risk in early onset complex AD and moreover has been shown to influence the expression of the PS...

M utations of presenilin 1 (PS1) account for up to 60% of early-onset familial Alzheimer’s disease (AD) (1). Because PS1 is a polytopic membrane protein, deciphering its topology is crucial to understanding its important functions. Hydropathy analysis of the PS1 primary amino acid sequence identified 10 hydrophobic regions (HR) [see figure 1A of Dewji et al. (2) in this issue of PNAS]. An eight...

BACKGROUND/AIMS To explore the potential value of myo-inositol (mIns), which is regarded as a biomarker for early diagnosis of Alzheimer's disease, in APP/PS1 transgenic (tg) mice detected by (1)H-MRS. METHODS (1)H-MRS was performed in 30 APP/PS1 tg mice and 20 wild-type (wt) littermates at 3, 5 and 8 months of age. Areas under the peak of N-acetylaspartate (NAA), mIns and creatine (Cr) in th...

BACKGROUND Pathogenic mutations in the presenilin 1 (PS1) gene leading to early-onset Alzheimer disease have been described in various populations. The different mutations are not distributed randomly in the PS1 protein but are clustered in some PS1 exons. OBJECTIVE To screen the PS1 gene in search of a potential mutation in a Spanish family with early-onset Alzheimer disease. METHODS Singl...

Mutations in the presenilin (PSEN1 and PSEN2) genes are linked to familial Alzheimer's disease (AD) and cause loss of its essential function. Complete inactivation of presenilins in excitatory neurons of the adult mouse cerebral cortex results in progressive memory impairment and age-dependent neurodegeneration, recapitulating key features of AD. In this study, we examine the effects of varying...

In this study we have analysed the genetic variation and phylogeography in a global sample of the cellar fungus Coniophora puteana, which is an important destroyer of wooden materials indoor. Multilocus genealogies of three DNA regions (beta tubulin, nrDNA ITS and translation elongation factor 1alpha) revealed the occurrence of three cryptic species (PS1-3) in the morphotaxon C. puteana. One of...

BACKGROUND Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphism (PS1-1) has been associated with doubling of the risk of sporadic late-onset Alzheimer disease (LOAD), in some, but not all studies. OBJECTIVE To genotype the PS1 intron 8 polymorphism in predominantly Hispanic families with LOAD to test for association and for linkage between this polymorphism and LOAD. DESIGN A fa...

The enzyme complex γ-secretase generates amyloid β-peptide (Aβ), a 37-43-residue peptide associated with Alzheimer disease (AD). Mutations in presenilin 1 (PS1), the catalytical subunit of γ-secretase, result in familial AD (FAD). A unifying theme among FAD mutations is an alteration in the ratio Aβ species produced (the Aβ42/Aβ40 ratio), but the molecular mechanisms responsible remain elusive....