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Alzheimer's research is a field in constant flux; no unifying theory of Alzheimer's biochemistry goes unchallenged, there are a great many such theories coming and going, and much remains to be discovered or proven. Conversely, so much money flows into Alzheimer's science that new results are constantly emerging to sway the picture in one direction or another. This is science at its messiest, which is usually also where it is most interesting, and most likely to soon deliver a firm, defensible theory.
A large fraction of the Alzheimer's research community focuses in some way on forms of amyloid or other aggregates that build up in the brain: why is it there, what is the mechanism by which it causes harm, how can we get rid of it safely, is it a cause or secondary marker of other harmful mechanisms, and so forth. On that topic, I noticed an interesting article from earlier this month that places Alzheimer's in a spectrum with other, similar neurodegenerative conditions:
Studies demonstrate link among Alzheimer's disease, Down syndrome and atherosclerosis
all Alzheimer's disease patients harbor some cells with three copies of chromosome 21, known as trisomy 21, instead of the usual two. Trisomy 21 is a characteristic shared by all the cells in people with the birth defect Down syndrome as well. This earlier work demonstrated that Alzheimer's disease could be considered a late onset form of Down syndrome.
By age 30 to 40, all people with Down syndrome develop the same brain pathology seen in Alzheimer's disease, including a nerve-killing buildup of sticky amyloid protein clumps.
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Dr. Potter and his colleagues now show that the Alzheimer's-associated amyloid protein is the culprit that interferes with the microtubule transport system inside cells. The microtubules are responsible for segregating newly duplicated chromosomes as cells divide. ... When the microtubule network is disrupted, chromosomes can be incorrectly transported as cells divide and the result is new cells with the wrong number of chromosomes and an abnormal assortment of genes.
If you read the rest of the article, you'll see that researchers can draw links between other common age-related conditions known to accompany Alzheimer's and damage to the microtubule network. This network is involved in transporting all sorts of important biochemicals around the cell - not just chromosomes. This implies that its widespread disruption in the body might be capable of causing all sorts of issues. But that theorizing needs more supporting science, such as a viable way to interfere in this process of microtubule damage, and then a demonstration that such a therapy in fact improves matters.
A competing theory for linking together the risk of suffering Alzheimer's and other common diseases of aging relates to fat, insulin metabolism, and lack of exercise. There, Alzheimer's is viewed as a form of diabetes, yet another of the many unpleasant consequences of metabolic dysfunction brought on by being overweight and sedentary for many years:
Insulin disappears early and dramatically in Alzheimer's disease. And many of the unexplained features of Alzheimer's, such as cell death and tangles in the brain, appear to be linked to abnormalities in insulin signaling. This demonstrates that the disease is most likely a neuroendocrine disorder, or another type of diabetes.
The microtubule version of a theory to explain the known association between risk of diabetes and risk of Alzheimer's involves problems in the transport of required biochemicals in the insulin signaling network:
key proteins - including insulin receptors and receptors for brain signaling molecules - are also likely locked inside cells when the [microtubule] transport system is damaged by amyloid or other factors. "The insulin receptors are needed to get blood sugar inside the cell where it can be used for energy. The nerve cell signaling receptors help promote memory and learning," Dr. Potter said. "So, if these receptors are unable to function properly, it may lead to diabetes and problems with learning and memory."
Hopefully this gives you a small taste of what almost all areas of Alzheimer's research look like at this time: a great deal of evidence and change, a great many ideas and competing viewpoints.
 Granic A, Padmanabhan J, Norden M, & Potter H (2009). Alzheimer A{beta} Peptide Induces Chromosome Mis-Segregation and Aneuploidy, Including Trisomy 21; Requirement for Tau and APP. Molecular biology of the cell PMID: 20032300
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Posted by Reason
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