More Insight on Inflammation and Alzheimer's Disease

This weeks edition of ALZForum reported on an interesting study correlating mid-life peripheral inflammation with subsequent cognitive decline.  We discuss the (incompletely) understood role of inflammation in the development of AD in Beating the Dementia Monster.  Consistent with what we said, the article said that diet and exercise are some of the best ways for controlling inflammation.  (Especially, stay away from fast food!)

The study has been following a cohort of more than 12,000 people for 30 years, testing their blood for proteins associated with inflammatory processes and correlating the findings with cognitive test results.  The upshot is that people who displayed evidence of inflammation in mid-life were significantly more likely to experience cognitive decline 20 years later.  The discussion in the article correlated the cognitive decline with the development of AD.  Tests also found increased presence of the beta-amyloid and tau proteins that are markers for AD.

The study warns to be careful about confusing correlation with causation.  They could not rule out the possibility that the inflammation was actually a reaction to the disease process, not a result of it.  They also said that measuring these proteins would be a poor way to predict AD risk, since there are many proteins involved, and they tend to have non-specific origins.

Not discussed but worth thinking about is the tie in with the ApoE4 gene variant.  This is what genetic testing services look for when predicting your risk for developing AD.  Some believe that enzymes (proteins) synthesized from the design specified by the ApoE gene play a role in controlling inflammation in the brain.  Enzymes synthesized from the ApoE4 variant may do a poor job in aiding the body's ability to control inflammation.   There is no evidence from the article that they controlled for the presence of the ApoE4 gene variant, but I'm left wondering if poor performance of the enzyme from this gene in fighting inflammation could be why they detected the inflammation byproducts. 

So my take:

ApoE4 gene variant results in enzyme -> enzyme does a poor job of controlling inflammation -> inflammation results in the presence of marker proteins in midlife ->  inflammation triggers AD -> AD disease process causes cognitive decline -> disease process generates more beta-amyloid and tau proteins

The study was The Atherosclerosis Risk in Communities (ARIC) cohort study.  It began with a cohort of 15,000 adults aged 45 to 65 from cities around the U.S.  More than half the participants are women, and almost a third are black.  The cohort was whittled down to 12,336 based on health and other factors that might confound the study.