People with Alzheimer’s disease and their loved ones are anxiously awaiting the next generation of Alzheimer’s treatments – drugs that will not just treat the symptoms but also stop or reverse the cause. However, no new drugs have been approved since 2003 due to the failure of at least 10 experimental treatments in clinical trials.
One of the most recent disappointments has been Bapineuzumab®, a promising monoclonal antibody infusion that targets the beta-amyloid tangles that are the physical hallmark of Alzheimer’s. Despite clearing away 25% of plaques in the brains of participating patients, no clinical benefit was observed [1].
For many scientists, though, this latest letdown is not all that surprising. While the appearance of protein tangles and plaques in the brain have been considered a key part of the disease process for decades, a number of researchers have found that people with more Alzheimer’s plaques do not necessarily have worse dementia symptoms [2-4]. This suggests that something other than amyloid plaques and tangles contribute to the development of Alzheimer’s.
Several groups of researchers believe that it is amyloid clumps (known as oligomers) that mess up proper brain cell function in people with Alzheimer’s, not the amyloid plaques [5-8]. To test this theory, researchers at Mount Sinai School of Medicine recently created a mouse that only develops oligomer “clumps” (without developing any sort of brain plaques) as they age.
In a study published online in April, the researchers discovered that mice that only develop protein clumps were just as impaired by the symptoms of Alzheimer’s as mice that develop both plaques and clumps [9]. In addition, the researchers found that when a gene that converted oligomers into plaques was introduced, the mice did get any worse than they were before.
These results show that the brain damage and memory issues associated with Alzheimer’s disease begins with oligomer clumps, not with the amyloid plaques previously singled out by researchers. Armed with this new understanding of the disease process, scientists will hopefully have the ammunition they need to develop the next generation of treatments Alzheimer’s patients and their families are eagerly waiting for.
References:
1. Rinne JO, Brooks DJ, Rossor MN, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9(4):363-372.
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7. Zhao WQ, De Felice FG, Fernandez S, et al. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB J. 2008;22:246-260.
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9. Gandy S, Simon AJ, Steele JW, et al. Days-to-criterion as an indicator of toxicity associated with human Alzheimer amyloid-beta oligomers. Ann Neurol. 2010;In press.
