This has been a big week in Alzheimer's news as scientists put together a clearer picture than ever before of how the disease affects the brain. Three recently published studies have detected the disease with new technologies, hinted at its prevalence, and described at last how it makes its lethal progress through the brain.

The existence of two forms of Alzheimer's—early- and late-onset—has long baffled scientists. Of the estimated five million Americans who suffer from Alzheimer's, only a few thousand are diagnosed with an early-onset form of the affliction, which affects people before the age of 65. This rare early-onset form is thought to be hereditary and scientists have associated multiple genetic mutations contributing to its occurrence. Late-onset Alzheimer's, although more common, has been the bigger mystery. One variant of the APOE gene-—sometimes known as the Alzheimer's gene—is linked to the late-onset disease. But the APOE gene, unlike dominant early-onset genes, does not determine whether a person will ultimately have dementia.

Now there's evidence that late-onset Alzheimer's has a genetic basis similar to that of early-onset Alzheimer's. By sequencing select genes associated with the latter, along with frontotemporal dementia, researchers at Washington University in Saint Louis and other institutions found that patients with late-onset Alzheimer's carry some of the same genetic mutations as those with the early-onset form. The evidence, published on Wednesday in PLoS ONE, bolsters the argument that the forms of Alzheimer's that appear at different life stages should be classified as the same disease. As to why the disease appears earlier in some cases, the scientists speculated that those patients diagnosed relatively early in life carry more genetic risk factors for the disease.

This study's use of rapid genetic sequencing, the authors noted, may provide a model for more precise identification of dementias. Within the study, the researchers identified patients who may have been misdiagnosed as having Alzheimer's; the genes of these patients suggested that they had another type of dementia. Given the heritable component, patients with a family history could be screened to detect and diagnose Alzheimer's early.

Other genetic research unveiled in the past week or so has shed light on the biological processes that underlie how Alzheimer's affects the brain. Certain mutations may lead to an increased production of a protein called amyloid beta in the region of the brain that creates memory. This excess amyloid beta, naturally secreted by brain cells, then becomes a complex called an oligomer. These oligomers may interrupt the signals transmitted between neurons. As in other neurodegenerative diseases like Parkinson's or Huntington's, the spread of oligomers appears to be driving the disease process.

Oligomer-linked diseases are relatively common, in part because oligomers can also play an essential biological role in the brain. A recent investigation using fruit flies reveals that the presence of a specific oligomer is actually required for the flies to form long-term memories.

In an early stage of Alzheimer's, the naturally secreted amyloid beta protein builds up as oligomers in the brain, which then go on to form larger aggregates called plaques. Later in the disease, another aberrant form of a protein called tau starts to build up, in the entorhinal cortex. Normally, tau helps provide structure crucial to neuron functioning. The buildup of tau, however, causes the protein to tangle and eventually kill brain cells. What was unknown until recently, however, was how the tau protein spreads through different brain regions.

3 Comments

1. 1. sparcboy in reply to JamesDavis 08:15 AM 2/6/12

   Well, since you politicized this, the drug companies stand to make hundreds of millions of dollars if they find a cure or substantial treatment. And since Republicans are pro-business, maybe you should hope the Republicans do take control.
   
   Life sure would be a lot easier if it were as black and white as some perceive.

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2. 2. bobbydelray 08:59 AM 2/6/12

   First, thanks to Scientific American and Daisy Yuhas for publishing this article.
   
   As is pointed out in the article, Alzheimer's research continues to advance. The pace of research, however, is slow due to inadequate funding. Articles like this one are important because they do raise awareness.
   
   An increase in funding would likely help scientist to find an effective treatment sooner rather than later.
   
   Right now, the best possibility is the discovery of a drug that could work in the way that "statins" do to lower cholesterol and stave off heart disease.
   
   In other words, stop or slow down the increase of Abeta in the brain.
   
   The best alternative right now would be to shift some of the already outstanding government funding to Alzheimer's research.
   
   The announced goal of stopping Alzheimer's by 2025 is unlikely to happen given the current levels of research funding.
   
   The question, would an all out funding effort now, save the taxpayers billions or even trillions of dollars in the future? Of course, the savings in family misery cannot be calculate in dollars and cents.
   
   Soon, every American will fall into one of two categories: suffering from Alzheimer's, or knows someone that is suffering from Alzheimer's.
   
   Bob DeMarco, Founder
   Alzheimer's Reading Room
   http://www.alzheimersreadingroom.com/

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3. 3. Famer-PhD in reply to bobbydelray 01:09 PM 2/6/12

   Please observe that there is no proof for a clear cause-and-effect between cholesterol (as such) and heart diseases, in the same way that there is no proof for a clear cause-and-effect between beta-amyloid (as such) and Alzheimer’s disease.
   
   What we have is a “significant association”, which means that beta-amyloid has to be present in the brain for someone to be diagnosed with Alzheimer’s disease. But bear in mind that beta-amyloid can also be found in the brains of cognitive healthy individuals and a large number of individuals suffer from Alzheimer’s-like dementia without it. Since it seems to be non-causative, removing it would probably make no difference on the onset or progression of the disease.
   
   People often talk about causes and associations as if they are real facts – our beliefs are defined by their oversimplifications – and we think we understand how something works and how all those shards of fact fit together when in reality, we don’t.
   
   We need to change our focus and learn how to understand the mechanism as a whole, not just the parts or their causal relationships.
   
   Twitter: @DFamer

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