Causes of Alzheimer's Disease

Scientists are searching for possible causes for Alzheimer's disease, which should lead to treatments to delay or even halt the dementing process. Efforts have focused on various neurotransmitter systems, especially the cholinergic system. Brain cells communicate through sending chemical as transmitters between cells. Acetyl Choline is one of these transmitters working between nerve cells responsible for alertness, attention, learning and memory. Rsearchers found evidence of prominent loss of cholinergic neurons in the basal parts of the front of the brain. Some of the latest discoveries have been in the area of molecular biology and genetics.

The fact that Down syndrome patients (a form of learning disability) invariably develop Alzheimer's disease changes in their brain and symptoms of dementia by their 40s prompted an initial focus on chromosome 21. Chromosome 21 is abnormal in Down's Syndrome (three copies of the chromosome exist in those patients instead of two as usual). Significant linkage to that chromosome 21 was discovered in some families with early-onset dementia but not in others.

Excitement in genetic research escalated when the gene coding for the amyloid precursor protein (APP) found in senile plaques was localized to the same chromosome 21 region. APP mutations, however, have been identified in only some families. More recent studies have shown that most early-onset parents show mutations of a chromosome 14 gene. Another form of early-onset Alzheimer's disease is represented by families of Volga German origin. For these families, chromosome 1 mutations have been identified.

Studies of the common late-onset disease (dementia beginning after 60 years of age) showed evidence for association with chromosome 19 region. The apolipoprotein E gene (APOE) was a candidate Alzheimer's disease susceptibility gene. APOE localized to the same region of chromosome 19 was identified in linkage studies.

APOE has three variants. Everyone inherits one variant from each parent, so that five common gene types are possible. The APOE-4 gene type increases risk and decreases age at which dementia develops. Susceptibility to Alzheimer's disease from APOE affects many races and has been confirmed worldwide.

Alzheimer's disease may be a diverse mixed condition. Familial Alzhiemer occurs when one or more first-degree relatives is affected or among a large number of kindreds. Sporadic cases of Alzheimer's disease with no relative with the same condition also appear in the general population. Patients with early-onset (65 years of age or younger) and late-onset dementia have clinical and biological differences among them. Other studies suggest sex differences in the disease expression. Interaction among age at onset, sex, and family history of dementia are possible.

Case-control studies have explored potential risk factors for Alzheimer's disease. Some studies have demonstrated risks, such as prior head trauma and depression. Factors that may reduce the risk for developing Alzheimer's disease are also being studied, including higher educational level, larger brain size, and use of anti-inflammatory or cholestrol lowering drugs (statin drugs).

In a sense, research in Alzheimer's disease is like solving a huge jigsaw puzzle: Although researchers are beginning to piece together a few corners, the puzzle is not yet solved.

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