OBJECTIVES Ample clinical and experimental evidence indicated that patients with Alzheimer's disease display a high incidence of cardiovascular events. This study was designed to examine myocardial histology, cardiomyocyte shortening, intracellular Ca(2+) homeostasis and regulatory proteins, electrocardiogram, adrenergic response, endoplasmic reticulum (ER) stress and protein carbonyl formation...

Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and γ-secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transf...

Mutations in presenilins are responsible for approximately 40% of all early-onset familial Alzheimer disease (FAD) cases in which a genetic cause has been identified. In addition, a number of mutations in presenilin-1 (PS1) have been suggested to be associated with the occurrence of frontal temporal dementia (FTD). Presenilins are highly conserved transmembrane proteins that support cleavage of...

Advanced age and mutations in the genes encoding amyloid precursor protein (APP) and presenilin (PS1) are two serious risk factors for Alzheimer's disease (AD). Finding common pathogenic changes originating from these risks may lead to a new therapeutic strategy. We observed a decline in memory performance and reduction in hippocampal long-term potentiation (LTP) in both mature adult (9-15 mont...

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific ...

BACKGROUND Mutations linked to early onset, familial forms of Alzheimer's disease (FAD) are found most frequently in PSEN1, the gene encoding presenilin-1 (PS1). Together with nicastrin (NCT), anterior pharynx-defective protein 1 (APH1), and presenilin enhancer 2 (PEN2), the catalytic subunit PS1 constitutes the core of the γ-secretase complex and contributes to the proteolysis of the amyloid p...

Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson's disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as ph...

BACKGROUND AND PURPOSE Presenilin1 (PS1) regulates Notch1 signaling activity, which liberates Notch intracellular domain (NICD). Notch activation promotes neural progenitor cell (NPC) self-renewal in the developing brain. In this study, we tested whether atorvastatin-induced NPC proliferation after stroke is mediated by PS1 and Notch1 activation. METHODS PS1 and NICD expressions were measured...

Mice carrying mutant amyloid-β precursor protein and presenilin-1 genes (APP/PS1 double transgenic mice) have frequently been used in studies of Alzheimer's disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer's disease is known to correlate with the amount of amyloid-β protein deposition and the number of dead neurons in the locus co...

The presenilin 1 (PS1) gene, located on chromosome 14, is the major gene involved in the autosomal dominant forms of early onset Alzheimer's disease (AD). In order to estimate the frequency of de novo PS1 mutations, we have sequenced the PS1 open reading frame in 13 clinically diagnosed patients with no affected relatives, who had developed AD before the age of 50. In one case with onset at 37 ...