Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer’s disease

Apolipoprotein E (apoE) ɛ4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer’s disease (AD). In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid β protein (Aβ). However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms by which apoE might enhance Aβ deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces lysosomal accumulation of Aβ and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other is the extracellular pathway in which apoE-containing lipoproteins are trapped by Aβ1–42 deposits mobilizing soluble Aβ peptides and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest a chaperone-like function for the apoE molecule. Received 4 February 1999; received after revision 9 April 1999; accepted 23 April 1999     

Endothelin-1 synthesis reduced by red wine.

Statistical evidence of reduced coronary heart disease in areas of high wine consumption has led to the widespread belief that wine affords a protective effect. Although moderate drinking of any alcohol helps to reduce the incidence of coronary heart disease, there is no clear evidence that red wine confers an additional benefit. Here we show that red wines strongly inhibit the synthesis of endothelin-1, a vasoactive peptide that is crucial in the development of coronary atherosclerosis. Our findings indicate that components specific to red wine may help to prevent coronary heart disease.     

Oenology: red wine procyanidins and vascular health

Regular, moderate consumption of red wine is linked to a reduced risk of coronary heart disease and to lower overall mortality, but the relative contribution of wine's alcohol and polyphenol components to these effects is unclear. Here we identify procyanidins as the principal vasoactive polyphenols in red wine and show that they are present at higher concentrations in wines from areas of southwestern France and Sardinia, where traditional production methods ensure that these compounds are efficiently extracted during vinification. These regions also happen to be associated with increased longevity in the population.     

15-Hydroxyprostaglandin dehydrogenase and hexokinase in spontaneously hypertensive rat kidney

Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.