128 However, the Syst-Eur study found that, use of a calcium-chan

128 However, the Syst-Eur study found that, use of a calcium-channel-blocking agent reduced the incidence of AD in older adults with isolated systolic hypertension.129 In addition to the hypothesized association between hypertension and the development, of AD, the past few years have seen a selleckchem CHIR99021 dramatic increase in the literature on the potential link between cholesterol levels and the development Inhibitors,research,lifescience,medical of AD. Several animal studies have found hypercholesterolemia to accelerate AD amyloid pathology,130,131 and cholesterol was observed to modulate the membrane disordering

effects of β-amyloid in the hippocampi of AD patients.132 The apolipoprotcin E (APOE) susceptibility gene for AD encodes for the APOE Inhibitors,research,lifescience,medical protein, which, among other things, is implicated in the transport of plasma cholesterol. Recent studies have also found increased scrum cholesterol levels to be associated with presence of the ε4 allele in AD patients.133-137

Some studies did not observe this association,138 and still others suggest, that the ε4 allele is independently Inhibitors,research,lifescience,medical associated with hypercholesterolemia and development of AD.139 Overall, however, these findings have led investigators to hypothesize a relationship among heart disease, cholesterol levels, and the development, of AD.119,131 Wolozin et al140 recently reported a decrease in the prevalence of AD to be associated with the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and a placebo-controlled clinical trial of the HMG-CoA reductase inhibitor, Lipitor® (atorvastatin calcium) is currently ongoing in patients with mild-to-moderate AD. It is interesting to note that estrogen has a positive impact, on lipoprotein levels and enhances cerebral blood flow, and several Inhibitors,research,lifescience,medical investigators have proposed that these physiological. benefits of estrogen may account for its association with reduced AD risk. Similarly, G biloba

is noted to protect, Inhibitors,research,lifescience,medical against ischemic damage, and may thus have benefits on cognition in AD patients. Methodological and conceptual Drug_discovery issues regarding therapeutic approaches to Alzheimer’s disease While this is an exciting time for the development of pharmacological approaches to AD, overall, the results of initial randomized clinical trials of agents such as estrogen and anti-inflammatory drugs have been somewhat disappointing. There are several important, conceptual and methodological issues that significantly impact the interpretations we can draw from the findings of many clinical trials in AD. First, given the complexities of the pathophysiological Imatinib Mesylate chemical structure mechanisms that appear to be involved in the development, of AD, it is unlikely that treatments targeting any one neuropathological pathway will be successful. Neuro-pathological heterogeneity may impact drug mechanisms and various pathophysiological mechanisms may interact to produce AD.

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