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RESEARCH BRIEFS
Lack of ApoE Lowers Blood-Brain Barrier, May Raise Alzheimer's RiskThe observation by 19th century bacteriologist Paul Ehrlich that certain dyes pass from the blood into all tissues except the brain was the first indication of the specialized barricade that separates the circulation from the brain. The blood-brain barrier arises from extremely tight intercellular junctions that can be crossed only by lipid mediation or catalyzed transport. Many questions remain, however, about its makeup and the consequences of its breakdown. Now HMS researchers have identified a protein that shores up the barrier. When the molecule, apolipoprotein E (apoE), is absent, the barrier becomes especially porous, making the brain vulnerable to trauma and possibly Alzheimer's disease. ApoE is a serum protein that binds and transports lipids through the bloodstream. Denisa Wagner, HMS professor of pathology at the Center for Blood Research and senior author of the study, observed that mice deficient in both apoE and certain endothelial adhesion molecules often die following birth-related hemorrhage and trauma to the head. "We wondered whether apoE might be important for the integrity of the brain's vasculature," she said. To test this, colleagues Nassia Methia, former research fellow in pathology, and Patrick André, research fellow in pathology, measured leakage of Evans blue dye from blood vessels into the cortex. Seventy percent more dye leaked into the brains of apoE-deficient mice than those of their wild-type counterparts. Following injury to the cortex, normal mice healed within a week while the brains of apoE-/- mice became even more leaky than before and remained so. Although apoE-deficient mutants have elevated levels of cholesterol, this alone does not explain the findings. When apoE-deficient mice were fed a "Western" diet, high cholesterol further aggravated leakage. According to Wagner, this study, published in the December Molecular Medicine, and two others published recently suggest links between apoE, an impaired blood-brain barrier, and Alzheimer's. Major risk factors for the disease, such as brain injury, age, and high cholesterol, are precisely those that aggravate the increase in blood-brain barrier permeability associated with apoE deficiency.
Both Experience and Training Build Expertise in HIV CareHands-on experience with HIV and AIDS patients may be just about as important as infectious-disease specialty training when it comes to physician expertise in caring for these patients, a report from the HMS Department of Health Care Policy suggests. In the January Journal of General Internal Medicine, Bruce Landon and colleagues provide the first national data on the relationship between specialty training and specialization and physician knowledge and referral practices. Landon, HMS assistant professor of health care policy, co-authored the report with Paul Cleary, HMS professor of medical sociology in the Department of Health Care Policy, and other investigators. The researchers surveyed 379 doctors who served as principal HIV physicians for patients in the HIV Costs and Services Utilization Study. They categorized physician respondents as either infectious disease (ID) specialists or generalists (including a few non-ID specialists) based on formal training and as self-identified HIV experts or nonexperts. Then they tested respondents on knowledge of HIV treatment practices and asked how often the physicians referred HIV patients to other providers. Self-identified HIV experts from general medicine scored similarly to ID-specialist experts on the knowledge test, averaging 8.5 and 9.0 questions correct out of 11, respectively. By contrast, scores for physicians who did not consider themselves experts averaged 7.8 for ID specialists and 6.5 for generalists. Physicians treating more HIV patients also scored higher. When asked about a variety of situations in which they would refer HIV patients to another provider, ID-specialist experts and generalist experts also gave similar responses. The authors note that "physicians not trained in [infectious diseases] can, by virtue of interest, clinical experience, CME activities, and other methods of self-education ... develop similar levels of HIV expertise" to ID specialists. --Tom Reynolds
Epstein-Barr Virus Linked to MSHSPH researchers report new data linking Epstein-Barr Virus (EBV) with the risk of multiple sclerosis, adding to evidence implicating the virus in a disease that afflicts more than a million people worldwide. Alberto Ascherio, HSPH associate professor of nutrition and epidemiology, and coworkers report that elevated levels of antibodies to certain EBV antigens are associated with as much as a fourfold greater risk of developing MS. The virus infects up to 95 percent of the general population, persisting in its host for life. At least one study has correlated this reactivation with MS-associated episodes of neural inflammation in the relapsing-remitting form of the disease. What is new about the present study is that the researchers were able to measure significantly elevated levels of antibodies to EBV in blood samples collected from women up to six and a half years before they had been diagnosed with MS. Of the 144 participants who had MS (and who were matched to 288 healthy controls), eighteen had given blood before developing neurological symptoms. The authors point out that elevated antibody titers could represent an early preclinical manifestation of the disease, and would thus not be causative, though they found it significant that similar results were obtained regardless of the time between disease onset and blood collection. The statistical nature of the study's findings also concerned Donald Gilden of the University of Colorado, who, in an editorial accompanying the study, published in the Dec. 26 Journal of the American Medical Association, wrote "Although the cause of MS is not likely to be found under the EBV lamppost, the search for a viral cause of MS must continue." HMS professor David Hafler has proposed that MS is a syndrome of diseases with distinct etiologies. Ascherio said, "The microorganisms that are responsible for MS have remained elusive. Our results suggest that Epstein-Barr may be the culprit, or at least, one of the culprits." --Anne Mahon |
