Whassup w/ apolipoprotein ApoE Alzheimer's research genetic factors

[Guest guest]

I "stole" this from medceu, that I'm getting continuing education units from-- I got my RN license back after 8 years of "SSDI disability for bipolar".

Somebody please tell me the mito docs are familiar with this testing and are using it with mitochondriacs. If not, get off the stick, guys! I could get in trouble for reprinting this... well, I have an excuse, I have Add, bipolar, migraines, cvs, muscle aches and pains, etc. and just turned in hair for testing!

Hugs, Kt

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Genetic Factors

The genes for the apolipoprotein ApoE which has been studied for years as a risk factor for heart problems has become a recent target for Alzheimer’s research. ApoE normally plays a role in the distribution of cholesterol for repairing nerve cells during development and after injury. The gene for ApoE comes in three possible types: ApoE2, ApoE3, and ApoE4; people inherit a copy of one type from each parent. Apo4 is a risk factor for Alzheimer’s disease. ApoE2s and E3 seem to have protective qualities that help to maintain nerve-cell structure.

The ApoE4 does not have this protective capability. E4 also binds to beta amyloid, the protein that forms the core of Alzheimer’s plaques and is thought to destroy nearby brain cells. Therefore, people who carry two copies of the E4 gene do not have the protection of the E2 or E3 gene have the highest risk for Alzheimer’s disease. People who have two copies of the E2 gene have the best protection against Alzheimer’s disease. In people without E4 , there is a 20% risk of developing Alzheimer’s by age 75. With one copy of the E4 gene, the risk increases to 60%. With two copies of the E4 gene the risk is 90% which occurs in only 2% of the population. Not everyone with Alzheimer’s has an E4 gene and some people with an E4 gene do not exhibit signs of Alzheimer’s.

Researchers now believe they have found all three genes for early-onset Alzheimer’s on chromosome 1, 14, and 21 and are associated with proteins that relate to beta amyloid. Research in this area is hoped to lead to therapies that can prevent the development of these destructive plaques.

Diagnosis

Alzheimer’s disease is distinguished from other forms of dementia by characteristic changes in the brain that are visible only upon microscopic examination. These are neuritic plaques (chemical deposits consisting of degenerating nerve cells combined with a form of protein called beta amyloid) and neurofibrillary tangles (malformations within nerve cells) in areas that are important for memory and intellectual functions. It is still through the study of brain tissue at autopsy from a person thought to have Alzheimer’s disease that a definitive diagnosis of the disorder can be made. Another characteristic of Alzheimer's disease is the reduced production of certain brain chemicals, especially acetylcholine. Other reduced brain chemicals are norepinephrine, serotonin and somatostatin. All these chemicals are essential for normal communication between nerve cells.

At this time there is no single definitive diagnostic test for Alzheimer’s disease that can be performed on a living patient. A complete physical, psychiatric and neurological evaluation by physicians) experienced in diagnosing dementing disorders should be obtained.

This should include:

a detailed medical history

mental status tests

neuropsychological testing

blood work

spinal fluid tests

urinalysis

chest x-ray

electroencephalography (EEG)

computerized tomography (CT scan)

electrocardiagram (EKG).

Such an evaluation is essential to rule out treatable dementias. When this kind of detailed examination is done, the accuracy of the diagnosis of Alzheimer’s disease is about 90 percent.

Symptoms

Alzheimer’s disease has a gradual onset of symptoms which include: difficulty with memory and loss of intellectual abilities severe enough to interfere with work or social activities, confusion, language problems, poor or decreased judgment, disorientation in place and time and changes in behavior or personality.

The progression of these symptoms vary with the patient, but eventually progress to the point that the Alzheimer patients are totally unable to take care of themselves. The average length of the disease is 8 years, but has been known to last 25 years.

Treatment

Currently there are no proven preventive therapies for Alzheimer’s disease and no agents are consistently effective in preventing the progression of the disease. Good planning, and medical and social management can ease the burdens on the patient and family. Physical exercise and social activity are important as is proper nutrition. A calm and well-structured environment may help the patient to continue functioning. Intervention strategies and appropriate medications can lessen symptoms such as depression, agitation, anxiety, sleeplessness and improve participation in activities.

There are two FDA-approved drug treatments for Alzheimer's disease:

Cognex (also known as tacrine or THA) . This drug is an anticholinesterase inhibitor and is effective in some patients in the early stages of the disease, requires dosing of 4 times/day and monitoring for liver toxicity.

Donepezil is also an anticholinesterase inhibitor, has the advantage of once /day dosing and liver toxicity is not a problem.

Both these drugs increase the brain’s supply of acetylcholine, a neurotransmitter that is decreased in Alzheimer’s, and improves memory function for limited periods in some patients.

Through epidemiological research scientists have identified two kinds of drugs that may slow Alzheimer’s disease: estrogen and anti-inflammatory drugs. This research is not completely reliable because it is based partly on the recall of people with Alzheimer’s and only one small-scale study of an anti-inflammatory has been done. Controlled clinical studies are needed to confirm and add to these epidemiological findings.

Another group of drugs that are being investigated is the anti-oxidants, specifically selegiline and vitamin E and their combination. Selegiline or deprenyl is an FDA-approved therapy for Parkinson’s disease that increases the supply of dopamine, another neurotransmitter that is decreased in Alzheimer’s. Some

scientists believe that free radicals generated through oxidative mechanisms play a role in Alzheimer’s, cancer and many other diseases.

Prognosis

Alzheimer’s disease has a duration of two to over twenty years during which time the patient’s ability to function is diminished to the point of complete dependency and at present is always fatal.

During the progression of the disease the main focus should be on treating symptoms, making the patient as comfortable as possible and protecting the patient from his inability to care for himself. In addition, the caregivers need to seek outside support, advice and services during all the stages of the disease. In the advanced stages of the disease the Alzheimer’s patient will need 24-hour attention.

Services

Once a diagnosis of Alzheimer’s disease has been made the caregiver or patient should immediately seek out the local chapter of the Alzheimer’s Association that will identify local support groups and services available in the area.

The following are organizations that can be of help:

Alzheimer’s Association

919 North Michigan Ave., Suite 1000

Chicago, IL 60611

Internet Address: http://www.alz.org/

This organization (with more than 3000 support groups and 220 local chapters nation wide) will provide names of local chapters, fact sheets and advice. It also provides information about Safe Return, a program for wandering Alzheimer’s victims. Their Medical and Scientific Affairs department answers questions on recent drug therapies.

Alzheimer’s Disease Education and Referral Center

PO Box 8250

Silver Spring, MD 20907-8250

Internet Address: http://www.cais.com/adear/

This organization was set up by the National Institute on Aging. It provides clinical trial and other information.

References:

1. Scientific American Medicine, July 1997, 11:XI Alzheimer’s Disease and the Dementias (CD-ROM)

2. Isselbacher K, Braunwald E, J, J, Fauchi A, Kasper D, Eds: on’s Principles of Internal Medicine, 13th Edition, McGraw-Hill, New York, 1994, (CD-ROM)

3. CONNECTIONS, Volume 6(1), Spring 1997, pp. 1-25.

4. Well-Connected, Report #2, August 31, 1995, Nidus Information Services, Inc.

5. Roses: AD: Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annual Review Medicine 47:387, 1996

6. Statement on use of apolipoprotein E testing for Alzheimer disease. American college of Medical .Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer’s disease. JAMA 274:1627, 1995

7. Corder EH, Saunders AM, Strittmatter WI, et al: Apolipoprotein E, survival in Alzheimer’s disease patients, and the competing risks of death and Alzheimer’s disease. Neurology 45:1323, 1995

8. Jobst KA, AD, Szatmari M, et al: Rapidly progressing atrophy of medical temporal lobe in Alzheimer’s Disease. Lancet 343:829, 1994

Credits:

This course has been prepared and written by MEDCEU staff writers and or MEDCEU affiliates.