Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Mutations in presenilins 1 and 2 (PS1 and PS2) account for approximately 40% of familial AD (FAD) cases. FAD mutations and genetic deletions of presenilins have been associated with calcium (Ca(2+)) signaling abnormalities. We demonstrate that wild-type presenilins, but not PS1-M146V and PS2-N141I FAD mutants...

OBJECTIVE To clarify the phenotypic heterogeneity in deposition of amyloid beta (Abeta) in the parenchyma and in cerebral vessels of the brains of the patients having presenilin-1 (PS1) mutations. Mutations in PS1 induce increased production of Abeta42(43), resulting in an enhanced overall deposition of Abeta protein within the cerebral cortex. METHODS Sequence analysis of the PS1 gene of DNA...

A chronic high fat Western diet (WD) promotes a variety of morbidity factors although experimental evidence for short-term WD mediating brain dysfunction remains to be elucidated. The amyloid precursor protein and presenilin-1 (APP x PS1) knock-in mouse model has been demonstrated to recapitulate some key features of Alzheimer's disease pathology, including amyloid-beta (Abeta) pathogenesis. In...

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAβPPswe/PS1ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer's disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SA...

Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer's disease (AD). Thus, there is interest in developing antioxidant therapies for the prevention/treatment of cognitive decline during AD. We reported previously that puerarin has antioxidative properties in vitro. Therefore, the aim of the pres...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the AβPP/PS1 transgenic mouse model is a commonly used experimental model to mimic the pathological and cognitive impairments in AD. As a classic method to evaluate spatial learning and memory, the Morris water maze is widely applied to study the cognitive deficits in rodent AD models. However, the assay procedure is relat...

The objective of this study was to assess the associations of presenilin 1 (PS1) 1/2, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D), and low-density lipoprotein receptor-related protein (LRP) C/T polymorphisms with the risk of Alzheimer's disease (AD) in the Chinese population. PS1 1/2, ACE I/D, and LRP C/T, which are commonly investigated polymorphisms, were evaluated to obtai...

Gamma-secretase cleavage is the final enzymatic step generating beta-amyloid via intramembranous cleavage of the amyloid precursor protein (APP). Presenilin (PS), initially identified as a gene in which mutations account for the vast majority of early-onset autosomal dominant Alzheimer's disease, is a major component of gamma-secretase. Enzymatic activity also depends on nicastrin, Aph-1, and P...

WT human APP 695 ; SAMP8, senescence-accelerated mouse prone 8; PKB, protein kinase B; ADAM, A member of the disintegrin and metalloprotease; IHC, Immunohistochemistry. This article has not been copyedited and formatted. The final version may differ from this version. ABSTRACT Alzheimer' disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition and neur...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles. Dl-PHPB [potassium 2-(1-hydroxypentyl)-benzoate], has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia, and Aβ-induced animal models by inhibiting oxidative injury, neuronal apoptosis, and glial activation. The aim of the ...