Alzheimer's Research on Causes and Risk Factors - An Overview

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Topics:
- What causes Alzheimer's
- What is known about risk factors for Alzheimer's
- Biological processes underlying the disease: What are the primary biological characteristics of Alzheimer's disease


What causes Alzheimer's?

We still don't fully understand what causes Alzheimer's disease, but scientists are zeroing in on the answers. This is one of the most exciting - and most important - areas of research, because understanding the causes should lead to more targeted treatments and ways to prevent the disease.

Scientists generally agree that there is unlikely to be a single clear "cause" of Alzheimer's. It is more likely the result of a combination of inter-related factors, including genetic factors, which are passed along family lines of inheritance, and environmental influences, which range from previous head trauma to educational level to one's experiences early in life. Each of these "risk factors" is currently the subject of a great deal of research. A growing body of research is also helping to identify various "lifestyle factors," such as dietary habits, high blood pressure and high cholesterol, which may influence one's risk of Alzheimer's disease.

What is clear is that Alzheimer's develops as a result of a complex cascade of biological processes that take place over many years inside the brain.

Stunning progress has been made recently in unraveling this cascade, and scientists now have a much clearer picture of what happens to the brain when Alzheimer's strikes.


What is known about risk factors for Alzheimer's?

The answers to this central question are evolving as research provides more information. Right now, age is the primary risk factor for Alzheimer's, along with family history (discussed under genetics). More women than men have Alzheimer's, but this is likely because women generally live longer than men; the incidence by age is similar among men and women. Education level and previous history of head trauma are also generally agreed upon as probable risk factors for Alzheimer's. Estrogen replacement therapy after menopause and the use of certain groups of drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and cholesterol-lowering drugs called statins, may also impact Alzheimer's risk, according to a number of studies. Compelling new evidence is now indicating that other "lifestyle factors," such as one's dietary habits, high blood pressure and high cholesterol, may impact one's risk for developing Alzheimer's disease. The reasons why these factors increase Alzheimer's risk are unclear, but there are clues.

* Non Genetic Risk Factors
http://www.alzinfo.org/alzheimers-research-causes-nongenetic.asp

* Genetic Risk Factors
http://www.alzinfo.org/alzheimers-genetic.asp


Biological processes underlying the disease: What are the primary biological characteristics of Alzheimer's disease?

People with AD gradually suffer memory loss and a decline in thinking abilities, as well as major personality change. These losses in cognitive function are accompanied by changes in the brain, including the build-up of amyloid plaques and tau-containing neurofibrillary tangles, which result in the death of brain cells and the breakdown of the connections between them.

Amyloid plaques and neurofibrillary tangles are the primary hallmarks of Alzheimer's disease. Plaques are dense deposits of protein and cellular material outside and around the brain's nerve cells. Tangles are twisted fibers that build up inside the nerve cells. Scientists have known about plaques and tangles since 1906, when a German physician, Dr. Alois Alzheimer, first identified them in the brain of woman who had died after suffering paranoid delusions and psychosis. Intensive research efforts of the last two decades have revealed much about their composition, how they form, and their possible roles in the development of Alzheimer's disease. The deposition of amyloid in the form of plaques is thought by many scientists to trigger the cascade of events leading to Alzheimer's pathology. Amyloid now is believed to be a critical target for eventual treatment. The best evidence that amyloid causes the disease comes from the genetic studies in which mutations of APP, PS1, PS2 and APOE e4 (the genes so far identified as causing some cases of Alzheimer's) all facilitate amyloid accumulation. In both the public and the private sector, important efforts are underway to expand understanding of the amyloid deposition process,which helps to set the stage for the development of new and effective therapies.

Using both transgenic animal models and experiments in tissue culture, scientists now understand more about how amyloid is snipped out of APP, how amyloid aggregates into plaques, and how plaques might lead to the brain destruction of later stages of AD. Importantly, these discoveries are also facilitating discovery of ways in which plaque production may be slowed. Many leads are being pursued, including development of compounds to halt amyloid deposition at various steps along the pathway, or to prevent downstream harmful effects of amyloid deposits.

NIH- and industry-funded scientists have now provided evidence that one of the proteins (enzymes) that snip amyloid out of APP may actually be identical to one of the genes, presenilin 1, whose mutations can cause inherited early-onset Alzheimer's. Scientists from several pharmaceutical companies have also identified the other snipping enzyme. Now, more effective drugs to inhibit production of amyloid by these enzymes can be developed. Prototypes are being developed and tested for safety in industry-sponsored trials.

Sources:
National Institute on Aging, "Progress Report on Alzheimer's Disease 2001"
National Institute on Aging, "Alzheimer's Disease: Unraveling the Mystery"
National Institute on Aging, Fiscal Year 2004 Congressional Testimony and Budget Requests.