(AD) is one of the most devastating neuro-degenerative disorders characterized by the two pathological hallmarks of amyloid plaques and neurofibrillary tangles. Multiple environmental factors, such as diet and life style, along with genetic factors are all significant contributors. In addition, classic cardio-metabolic factors such as hypertension, stroke, diabetes and hypercholesterolemia incr...

β-amyloid (Aβ) is produced by the β-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer's disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism. The objective of this study was to determine the effect of RNA interference against BACE1 (shBA...

Cholesterol prevents Alzheimer’s lood vessels work best when they are clear of cholesterol. But neurons need cholesterol to maintain top form, according to Abad-Rodriguez et al. (page 953). With too little of this membrane lipid, neurons produce more of the Alzheimer’sassociated amyloid peptide (A ). The results are a warning that the effects of cholesterol-lowering drugs may need to be confine...

Cholesterol prevents Alzheimer’s lood vessels work best when they are clear of cholesterol. But neurons need cholesterol to maintain top form, according to Abad-Rodriguez et al. (page 953). With too little of this membrane lipid, neurons produce more of the Alzheimer’sassociated amyloid peptide (A ). The results are a warning that the effects of cholesterol-lowering drugs may need to be confine...

According to the amyloid cascade hypothesis, cerebral deposition of amyloid-β peptide (Aβ) is critical for Alzheimer's disease (AD) pathogenesis. Aβ generation is initiated when β-secretase (BACE1) cleaves the amyloid precursor protein. For more than a decade, BACE1 has been a prime target for designing drugs to prevent or treat AD. However, development of such agents has turned out to be extre...

BACKGROUND Cerebral amyloid angiopathy (CAA) refers to the deposition of β-amyloid (Aβ) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aβ deposition in leptomeninge. The cellular origin of angiopathic Aβ and the pathogenic course of CAA remain incompletely understood. METHODS The present study was aimed to e...

Amyloid beta protein (Abeta) is the principal component of neuritic plaques in Alzheimer's disease (AD). Abeta is derived from beta amyloid precursor protein (APP) by beta- and gamma-secretases. Beta-site APP cleaving enzyme 1 (BACE1) has been identified as the major beta-secretase. BACE2 is the homolog of BACE1. The BACE2 gene is on chromosome 21 and has been implicated in the pathogenesis of ...

Inactivity, obesity, and insulin resistance are significant risk factors for the development of Alzheimer's disease (AD). Several studies have demonstrated that diet-induced obesity, inactivity, and insulin resistance exacerbate the neuropathological hallmarks of AD. The aggregation of β-amyloid peptides is one of these hallmarks. β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) is th...

Although the role of APP and PSEN genes in genetic Alzheimer's disease (AD) cases is well established, fairly little is known about the molecular mechanisms affecting Abeta generation in sporadic AD. Deficiency in Abeta clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/beta-secretase may also be associated with the disease. We therefore investigated ch...