A Global Response to HIV / Statins Protect Against Alzheimer Disease

A comprehensive response to HIV could prevent 10 million AIDS deaths in Africa by 2020

One of the most urgent problems in HIV/AIDS policy is in deciding how best to allocate resources toward preventing new infections or treating infected individuals.

An analysis by Joshua Salomon and colleagues in the premier open-access journal PLoS Medicine, published online January 11, 2005, suggests that an exclusive focus on one or the other of these alternatives will yield minimal benefits—failing to integrate the two approaches could have a catastrophic effect on the global toll of HIV/AIDS by 2020.

In this modeling study the authors analyze the epidemic in sub-Saharan Africa (where three-fourths of deaths from AIDS occur). With no change in current levels of prevention and care, it is predicted that there will be 3.7 million new HIV infections and 2.6 million adults dying of AIDS in this region each year within the next two decades.

The authors predict that combining effective prevention and treatment efforts, however, could yield substantially greater benefits than the sum of the two alone—lowering projected new infections by 74% and projected annual mortality by half. These percentages translate into 29 million new infections and 10 million deaths averted between 2004 and 2020.

While treatment itself can be life-saving, long-term reductions in AIDS deaths will be achieved only if new infections are curbed. What is more, campaigns to expand treatment access in poor countries will only be sustainable if prevention efforts are strengthened at the same time. As the authors say: “Treatment can enable more effective prevention, and prevention makes treatment affordable. Sustained progress in the global fight against HIV/AIDS will be attained only through a comprehensive response.”

The published article will be accessible to your readers at:
http://www.plosmedicine.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0020016

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Healthy Cleavage: How Statins protect against Alzheimer Disease

Epidemiological studies suggest that statins, a class of cholesterol-lowering drugs, lower the risk for Alzheimer disease. How exactly statins and Alzheimer Disease are connected is not known, but a study by Sam Gandy and colleagues now suggests a possible mechanism.

Alzheimer disease is characterized by accumulation of amyloid deposits in the brain. These deposits are composed of amyloid-beta (Aâ) peptide, a protein fragment that is cleaved off from the amyloid precursor protein APP. APP can be cleaved in two different ways.

Amyloidogenic (“amyloid generating”) cleavage by an enzyme called beta-secretase yields “sticky” Aâ peptides that aggregate to form deposits, whereas non-amyloidogenic cleavage by alpha-secretases generates soluble peptides that do not form deposits.

Studies in animal models and cell culture suggest that statins might modulate APP processing and shift the balance toward “healthy” (non-amyloidogenic) cleavage.

In their quest to understand how statins affect APP processing, Gandy and colleagues focused on a molecule called ROCK, a kinase enzyme that had recently been implicated in APP processing. Working in mouse neuroblastoma cells, they confirmed that two different statins increased healthy cleavage of APP. When they then blocked ROCK, the effects were similar to those of the statins: an increase in healthy cleavage. On the other hand, when they added a super-active version of ROCK, they saw much less healthy cleavage, and adding statins didn’t improve the situation.

These findings suggest that statins influence APP processing, at least in part, by inhibiting the ROCK kinase. And independent of statins, ROCK might be a suitable target for drugs that promote healthy cleavage of APP.

The published article will be accessible to your readers at:
http://www.plosmedicine.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0020018