Profile of Professor Lee Makowski

By Sam LaRussa

Alzheimer’s disease is the sixth leading cause of death in the United States and is currently affecting somewhere around five million Americans. Despite its prevalence, very little is known biochemically about the nature of Alzheimer’s, and, because of this, treatment options are currently nonexistent and hard to research. The lab of Northeastern University’s own Professor Lee Makowski is currently working on research that might greatly further our understanding of this disease.

Dr. Makowski’s lab works primarily on developing techniques that use x-ray scattering in order to better characterize a variety of proteins. This research lends itself very well to looking into Alzheimer’s, as the disease has long been associated with plaques made of peptides (short chains of amino acids, like proteins) present in post-mortem examination of the brains of affected individuals. Despite this association, though, plaques have also been found during examination of the brains of individuals who had never exhibited symptoms of Alzheimer’s disease at all. Even more confusingly, the brains of individuals who did not have Alzheimer’s can possibly have more plaques present than the brains of individuals who had symptoms of the disease. Still, all individuals with Alzheimer’s have at least some plaques present.

In an attempt to explain these odd observations, Dr. Makowski’s lab has been working to determine whether the peptides present in harmful plaques are the same as those that don’t seem to cause Alzheimer’s. This is done by firing small, focused beams of X-ray radiation at plaques found in slices of brain tissue taken from both Alzheimer’s patients and individuals who did not have this disease. This high-energy X-ray radiation scatters upon hitting the plaques, and by looking at how it scatters, it is possible to determine information about the structure of the peptides that were targeted.

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Plaques observed in brain tissue of an Alzheimer’s disease patient[/caption]

With the information that Dr. Makowski’s lab has gathered so far, it appears that the plaques present in samples taken from Alzheimer’s-affected brains are different from those present in the brains of individuals that did not have the disease. Furthermore, the Alzheimer-linked plaques appear to be very homogenous, consisting of only one kind of peptide. The plaques that don’t seem to be linked to the disease seem to be much more heterogeneous, scattering X-rays in a way that suggests that they are formed out of a variety of peptides or proteins. If these data are correct, it could mean that there are two kinds of plaques that can form in an individual’s brain: malignant plaques that are homogenous and disease-causing, and benign plaques that have no link to Alzheimer’s. Furthermore, the observation that malignant plaques seem to be made out of only one kind of peptide makes strong suggestions in favor of the idea that these peptides come from one another. This, in turn, could lead to a better understanding of what causes the plaques to form in the first place.

Despite promising observations so far, Professor Makowski emphasizes that the results of this research are tentative, and are not yet complete enough to draw solid conclusions from. There is still more research that needs to be done, with different sample preparations and more solid data to produce. Still, it is a step in the right direction towards a better understanding of Alzheimer’s, a common, deadly and mysterious disease.