According to the Hopkins researchers who led the study, this initial research is essential to understanding why these differences occur and for future development of a vaccine or other preventive methods that could stop sexual transmission of HIV-1.

The couples in the study come from the Rakai Cohort, a Uganda-based population in a long-term study of HIV infection. The researchers tested each couple's viral RNA to determine which variants, or kinds of HIV-1 strain, were present in each man and woman. Variants of HIV-1 can be distinguished by differences in the gene (gp160) for their protein envelope. The findings showed that only a subset of HIV-1 variants in the initially infected partner was transmitted to the newly infected partner, and the predominant variant in males was not the kind that infected their female partners. And, women infected by men had a greater number of variants than men infected by women.

The selection of HIV-1 during sexual transmission: differences in gp160 diversity in male-to-female versus female-to-male transmission. Oliver Laeyendecker, Jordyn Gamiel, James Shepard, Xianbin Li, David Serwadda, Nelson Sewankambo, Fred Wabwire-Mangen, Francine McCutchan, Jonathan Toma, Wei Huang, Ronald Gray, Maria Wawer, and Thomas Quinn.

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So, our hypothesis is that in familial Alzheimer's disease ” or in disorders such as Down syndrome where beta-APP is overexpressed ” those defects cause early failure in cellular transport, he said. And those failures then stimulate further production of A-beta peptide, which may further poison the machinery.

Goldstein theorized that Alzheimer's disease might develop spontaneously in people without an overt genetic defect, as the transport machinery in their neurons breaks down with age. A person could have a predisposition to the disease, or it could just be that as time progresses, one person could by chance accumulate these blockages more than another, said Goldstein. And randomly, some people would accumulate more than others, enough to cross a critical threshold and tip the scale toward disease.

Goldstein emphasized that any application of these findings to potential diagnostic tests or new therapies remains speculative at this time. However, if tracers could be developed that would reflect transport function, there could be imaging methods that might be helpful for diagnosis, he said. And, if these findings continue to hold for humans, the transport machinery could be a target for drugs to preserve that machinery.

The researchers plan to continue their exploration of the transport machinery's involvement in Alzheimer's pathology by using human embryonic stem cells to differentiate into neurons in culture. Their goal is to alter those neurons genetically by introducing mutations know to cause Alzheimer's disease in people, to then test for transport defects, and then study whether those defects produce pathology similar to that seen in Alzheimer's. One of the questions they will also ask is whether amyloid plaques poison the transport machinery. If the experiments do, indeed, confirm the predictions of the transport hypothesis, then neuronal cultures could prove valuable in testing diagnostic and therapeutic approaches, said Goldstein.

The researchers are also analyzing more brain tissue samples from humans with Alzheimer's disease, to confirm their findings of the early transport defects and their effects on neuronal death.

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