Mutations in the presenilin-1 (PS1) gene are independent causes of familial Alzheimer's disease (AD). AD patients have dysregulated immunity, and PS1 mutant mice exhibit abnormal systemic immune responses. To test whether immune function abnormality caused by a mutant human PS1 gene (mhPS1) could modify AD-like pathology, we reconstituted immune systems of AD model mice carrying a mutant human ...

Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are associated with early-onset familial Alzheimer's disease which displays an accelerated deposition of amyloid plaques and neurofibrillary tangles. Presenilins are multi-spanning transmembrane proteins which localize primarily to the endoplasmic reticulum and the Golgi compartments. We have previously demonstrated that PS1 exists...

BACKGROUND Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study a...

We report on the generation and phenotype of mutant alleles of multiple edematous wings (mew), the gene encoding the alpha PS1 subunit of the PS1 integrin of Drosophila. None of the six alleles examined makes detectable protein, and one allele results from a chromosome break near the middle of the translated sequence, so we are confident that we have described the null phenotype. In contrast to...

Presenilin mutations are responsible for most cases of autosomal dominant inherited forms of early onset Alzheimer disease. Presenilins play an important role in amyloid beta-precursor processing, NOTCH receptor signaling, and apoptosis. However, the molecular mechanisms by which presenilins regulate apoptosis are not fully understood. Here, we report that presenilin-1 (PS1) regulates the prote...

To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(-/-) mice that have a severe loss of LC neurons projecting to the hippocampus and neocortex. Testing spatial memory and hippocampal long-term potentiat...

Mutations in genes encoding the highly homologous proteins presenilin-1 and -2 (PS1 and PS2) are linked to the early onset of Alzheimer's disease (AD). Here, we report that polyclonal antibodies against Xenopus PSbeta (PS2), but not PSalpha (PS1), suppress the in vitro apoptotic activation of Xenopus egg extracts. To clarify the relationship between structural and functional differences in pres...

Neuroprotection of erythropoietin (EPO) following long-term administration is hampered by the associated undesirable effects on hematopoiesis and body weight. For this reason, we tested carbamylated-EPO (CEPO), which has no effect on erythropoiesis, and compared it with EPO in the AβPP/PS1 mouse model of familial Alzheimer’s disease. Groups of 5-month old wild type (WT) and transgenic mice rece...

Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ h...

T he amyloid precursor protein (APP) is the precursor to the amyloid β-protein (Aβ), which is the major constituent of amyloid plaques found in brains of individuals with Alzheimer’s disease (AD). Because amyloid (senile) plaques are one of the pathological hallmarks of AD, processing of APP and generation of Aβ from APP have been areas of intense study. Cloning of the APP cDNA in 1987 led to a...