Alzheimer’s Part I: Disease

Posted on September 22, 2007
Filed Under Health, Science |

In 1906 Alois Alzheimer a neuropathologist (or so they say) was the first to diagnose the disease which is named after him from a 55 year old patient Auguste D. Since for the most part, Alzheimer’s is a disease of the elderly, occurring in people over the age of 60, it was somewhat of a rarity in the 1900’s. However, with increasing lifespans Alzheimer’s became more prevelant.

Although there is still speculation as to how Alzheimer’s disease is caused, all explainations involve the observation of plaques (made of a protein called Beta amyloid) which are located outside of nerve cells known as neurons and neurofibrillary tangles (made of microtubules) which are found within these cells. This is where the speculation or problem with how Alzheimer’s is caused comes into play. Are the plaques and neurofibilarry tangles which are found in Alzheimer patients the cause or a consequence of the disease?

Adding to deciphering the disease is the fact that Alzheimer’s appears to have a familial and non-familial form. The cause of the familial form is known (Early onset familial Alzheimer’s). However, this form of Alzheimer is only responsible for about 5% of Alzheimer disease with symptoms occuring from age 45 to 65. In the familial form, enzymes known as secretases cleave amyloid as part of there normal function, these secreteases are produced by chromosome 21, however, this enzyme is dysfunctional in Alzheimer patients resulting in an over-production of a Beta amyloid form of protein. In addition, the enzymes that cleave amyloid are further regulated by other genes known as presenilins which can also become dysfunctional resulting in the same process (a build-up of Beta amyloid) leading to the familial form. Alzheimer patients with the build-up of Beta amyloid have plaques which are located in areas of the brain responsible for memory along with neurofibrillary tangles. This also correlates with enlarged ventricles, reduction in brain tissue (death of nerve cells).

Given this information, there is a strong belief by some scientists that Beta amyloid is responsible for the non-familial form of the disease. That is, that Beta amyloid is directly responsible for the disease and not a consequence of the disease. However, there are others who believe that another gene known as APOE4 an Alzheimer susceptibility gene is responsible for Alzheimer’s.

There are several forms of the gene APOE, APOE3 is the most common form, but individuals who have APOE4 have a significantly increased risk of getting Alzheimer’s disease. APOE can apparently bind secretases therefore, it would follow that a lack of secretases can result in a build-up of plaques. APOE can apparently anchor Beta amyloid plaques, so again is it Beta amyloid, APOE or both or something else. By the way, that something else could be a protein known as Tau, Tau regulates microtubules within nerve cells, Tau can become dysregulated resulting in the neurofibrillary tangles.

So the debate rages on as to what causes Alzheimer and several ways have been used to try isolate the problem. More exciting than the debate as to the “how” Alzheimer is caused, part II on Alzheimer’s will show some exciting evidence which may result in a novel treatment of the disease and why there is good reason to believe that one theory is correct.

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