To Solve Alzheimer’s Mystery, Better Biological Clues Sorely Needed

7/29/14Follow @alexlash

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an interesting test case.

Four decades after the U.S. declared a “war” on cancer, there have been battles won and plenty of advances, but no victory. The medical field has spent far fewer years with a similar focus on Alzheimer’s; it was only two years ago the Obama administration unveiled a national plan to find a cure by 2025.

I don’t think we’re on the brink of “controlling” Alzheimer’s. I think the best we can hope for is for researchers to make advances toward an eventual preventative—in particular by sharpening our understanding of the biomarkers of the disease in its earliest stages. (Earlier I discussed genetic clues. Below, I’ve highlighted recent developments in other main areas of biomarker research.) Before there’s a cure, society needs smaller but helpful ways to lessen the disease’s impact upon those already showing symptoms. If those things don’t happen, we’ll find ourselves instead on the brink of an abyss, into which many of our loved ones, friends, and colleagues are bound to fall.

Imaging

Researchers no longer need to wait for an autopsy to see the ravages of Alzheimer’s disease on a patient’s brain. Positron emission tomography (PET) scans combined with radioactive tracers now show the buildup of beta-amyloid plaques in living patients’ brains. The problem, however, is that the presence of plaques in the brain doesn’t always indicate Alzheimer’s disease. Approximately 30 percent of people with plaques never show symptoms. A second major protein implicated in Alzheimer’s, tau, forms abnormal tangles in diseased brains that are detectable on PET scans, and tau might be more closely associated with cognitive decline. A study discussed at the recent Copenhagen conference pointed toward that association. “Preliminary data suggest that tau in these brain areas is related to memory decline in normal older individuals,” Keith Johnson of Massachusetts General Hospital, the lead investigator, said at the conference. “This study demonstrates the potential for PET technology to be used for early detection, and to help pick participants for prevention trials and treatment trials that target tau.”

Tau imaging is also a big part of a new initiative built as a companion study to the A4 trial. Called LEARN, the study is funded by the Alzheimer’s Association’s largest grant ever. A4 is testing an anti-amyloid treatment in people with amyloid buildup but no Alzheimer’s symptoms. LEARN will enroll some of those who test negative for amyloid buildup, track their cognitive states, and test them for tau abnormalities, among other things.

Cerebrospinal Fluid

Researchers are also tapping into patients’ cerebrospinal fluid to measure the proteins floating around. Variations of beta-amyloid and tau are of keen interest, in part fueled by the realization that beta-amyloid plaques aren’t always correlated with dementia. Could the beta-amyloid still washing about in the spinal fluid be the problem? Some recent research implicates so-called “soluble oligomers”—or certain kinds of free-floating fragments—of beta-amyloid as the trigger that makes tau misfold, clump into tangles, and kill neurons. Acumen Pharmaceuticals of Livermore, CA, one of the few startups braving Alzheimer’s research, is creating a diagnostic to measure the beta-amyloid fragments in spinal fluid, and developing an antibody therapy to clear them. Its lead program was in Merck’s hands for several years but returned to Acumen in 2011. Acumen wants to put it into clinical trials by the end of 2016, said chief operating officer Bill Goure.

Blood

Some people can’t take any kind of needle, but for patients, drawing blood is a lot better than tapping spinal fluid. It would be cheaper, too. A blood test for Alzheimer’s biomarkers would be a big step forward. Researchers from a U.K. biotech, Proteome Sciences, and from King’s College London said in July they had isolated 10 proteins in the blood that seem to predict who with mild cognitive impairment would develop Alzheimer’s within a year. They gave it an accuracy of 87 percent and were careful to frame it as a “significant step” toward a test. But observers remain wary. Bristol-Myers Squibb biomarker specialist Holly Soares, who led a public-private project last decade to analyze the blood proteomics of people with Alzheimer’s, says work in the field in general has been promising and the field will “likely” develop many valid markers. About the Proteome/King’s College work, she only said via e-mail that it was “an independent work stream” from her group’s project. But in general, she said, “the difficulty lies in … Next Page »

Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco. Follow @alexlash

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  • Mike Mongan

    If the incidence of Alzheimer’s has been on the rise, it may be beneficial to look at what chemicals have risen in our environment, especially in our food supply. This assumes there is a cause to the disease. People have been “getting senile” for many decades, so there may be a genetic predisposition. But there may be chemical antagonists in our food and environment.

    I remember hearing that back in the 1940′s when I was a child, there were some 40,000 common chemicals in the American environment. That number has increased dramatically. The body and brain can only process and eliminate so many. It may be impossible to go back to a simpler time. That would not eliminate the problem. It may however be productive to begin to search for non traditional antagonists.

    There has been senility in my family. So far my brother and I , both in our 70′s, are fine thus far. I am a vegetarian and prefer organic foods and lots of vitamins. He has a more traditional but conscious diet. That may not be the clue. We grew up in a polluted city back then. But those were not today’s pollutants. My career was in manufacturing, his in banking.

    If the answer lies outside of the body, it can hopefully be identified. That would at least present some avoidance strategies for individuals to adopt.