Public Health and Genetics Information Series
What Is Alzheimer’s Disease?
Alzheimer’s disease (AD) is the leading cause of dementia, which is the loss of memory, reason, judgment or language so that it interferes with a person’s life, in those people over 65. AD causes the gradual loss of brain cells, called neurons. Neurons shrink as the brain ages and plaques, which are dense, deep deposits of protein, can buildup in neurons. When neurons die they are not replaced. AD disturbs the metabolism, communication and repair of neurons, which causes the nerve cells to stop working and eventually die. This cell death causes changes in memory, judgment, language skills, personality and behavior. The duration of AD varies from to 20 years. A person with AD will eventually need to be cared for in all aspects of their life. If the individual has no other illnesses the loss of brain function in AD will cause death.
An excellent review of
Alzheimer’s disease has been created by the Alzheimer’s Disease Education and
Vertical sections through a normal
(right) and a late stage Alzheimer’s brain (left) showing massive tissue
loss and enlargement of cavities. (From, Piecing Together Alzheimer’s by Peter H St George-Hyslop.
Vertical sections through a normal (right) and a late stage Alzheimer’s brain (left) showing massive tissue loss and enlargement of cavities.
(From, Piecing Together Alzheimer’s by Peter H St George-Hyslop.
What Is the Public Health Impact of AD?
Approximately 4 million people in the
What Causes Alzheimer’s Disease?
The exact cause of AD is still unknown however, researchers are beginning to understand what happens to the brain cells as a result of AD. The cause of Alzheimer’s disease is most likely a combination of many factors. Possible risk factors include, but are not limited to: age, family history of AD, genetic alterations, cardiovascular risk factors, oxidative damage by free radicals, inflammation, and brain infarction.
The Biology of AD
Alzheimer’s disease brains are characterized by the presence of beta-amyloid plaques and neurofibrillary tangles. All older people develop plaques and tangles, but a person with AD develop more.
Microtubules are the internal structural support in healthy neurons; they guide nutrients and molecules throughout the brain cell. A protein known as tau helps to make the microtubules stable. In individuals with AD, tau is chemically changed so that the protein pairs with other tau proteins to cause tangles. The microtubule therefore disintegrates and the neuron’s support system collapses. This may result in miscommunication between cells and later, cell death.
1) APP molecule 2) APP is snipped 3) Plaque develops
Plaques are made up of fragments snipped from a protein called APP (amyloid precursor protein). The fragments that have been snipped clump together to form a plaque (see figures above). The plaques develop in the hippocampus and in the cerebral cortex, which are specific regions of the brain.
How Are Genes Involved?
About 75 percent of Alzheimer’s disease cases are classified as sporadic, which means that no other blood relatives are affected. The precise cause of these cases is not known, but genetics may play a role in combination with other factors.
The other 25 percent of Alzheimer disease cases can be classified as hereditary, which means they are caused by altered genes and tend to occur in families. These hereditary cases are divided into early-onset AD, where symptoms of AD appear before age 65, and late-onset AD, where symptoms begin after age 65.
Early-onset AD usually affects individuals between the ages of 30-60. Early-onset cases comprise approximately 6-7% of all AD cases worldwide. About 7% of the early-onset cases are inherited (passed on through generations) and these cases are called Familial Alzheimer’s disease, or FAD. FAD is inherited in an autosomal dominant manner, which means only one copy of the altered gene is necessary to cause the disorder. Generally, a person affected with an autosomal dominant disease has one affected parent. Researchers have found three genes that are involved in FAD. A person affected with FAD usually has an alteration in one, but not all, of these genes:
1. Amyloid precursor protein (APP)- This gene is located on chromosome 21. If an individual has an alteration in the APP gene their illness is called Alzheimer’s disease, type I.
2. Presenilin 1 (PSEN1)- This gene is located on chromosome 14. If an individual has an alteration in the PSEN1 gene their illness is called Alzheimer’s disease, type 3.
3. Presenilin 2 (PSEN2)- This gene is located on chromosome 1. If an individual has an alteration in the PSEN2 gene their illness is called Alzheimer’s disease, type 4.
Late Onset AD
The genetic causes of late-onset Alzheimer’s disease are less defined. A gene that definitely causes late-onset Alzheimer’s disease has not been identified. However, a gene called apolipoprotein E (APOE) has been studied as a risk factor for the disease. Particularly, one form (or allele) of the APOE gene seems to increase an individual's risk for developing late-onset Alzheimer’s disease. Late-onset Alzheimer’s disease is also known as Alzheimer’s disease, type 2. This condition is most common in individuals over the age of 65. There are several APOE alleles. The epsilon 4 allele (or e4) is associated with an increased risk of late-onset Alzheimer’s disease. Carrying one APOE e4 allele nearly doubles an individual’s lifetime risk of AD. An individual who possesses one copy of the APOE e4 allele may develop Alzheimer’s disease an average of 5-10 years earlier than an individual without a copy of the APOE e4 allele. However, it is very important to note that inheriting an APOE e4 allele is not a guarantee that person will definitely develop AD. APOE e4 simply increases the risk of developing late-onset Alzheimer’s disease.
The other forms of the APOE gene are e2 and e3. The most common form of APOE is e3. There has been some evidence that shows the APOE e2 version may have a protective effect for risk of AD. In addition to Alzheimer’s disease the APOE gene has been associated with some cardiovascular disorders. Many individuals with familial hypercholesterolemia have two copies of APOE e2. Hypercholesterolemia is a condition in which a person has very high levels of cholesterol and is at high risk for stroke and heart attacks. Hypercholesterolemia is most likely influenced by more than one gene. Additionally, the e4 allele is a risk factor for coronary artery disease.
Genetic testing for AD
· Because of the rarity of APP, PSEN1 and PSEN2 mutations in patients with late-onset AD, testing for these mutations should be limited to those with early-onset AD or a strong family history.
· Relatives of people with documented gene alterations may require testing for family financial or personal planning.
· Presymptomatic testing should be carried out with extreme care and only after genetic counseling so that the individual is aware of the psychological aspects of testing for an incurable illness.
· There may also be consequences in employment and health insurance, which the individual must understand.
· Additionally, a positive test may indicate other family members at risk who have not undergone genetic counseling and do not desire genetic testing.
· APOE e4 testing in individuals that do not show signs of Alzheimer’s disease should not be conducted at this time.
How is Alzheimer’s Disease Diagnosed?
A definitive diagnosis of AD is available only after death, when an autopsy may be completed. However, doctors are able to get a fairly accurate diagnosis in a living person by:
· A detailed family history
· Physical and neurological exams and laboratory tests
· Computerized tomography (CT) scan or magnetic resonance imaging (MRI)
· Additional neuropsychological testing
Specific criteria have been established by physicians in order to make a probable diagnosis of AD:
· Dementia confirmed by clinical and neuropsychological examination
· Progressive worsening of memory and other mental functioning
· No disturbances of consciousness (no blacking out)
· Symptoms began between ages 40-90
· No other disorders might account for dementia
Furthermore, an early, accurate diagnosis of AD can assist in helping patients and their loved ones plan for the future. An early diagnosis allows time to discuss alternatives in care while the patient is able to participate in such decisions. Early diagnosis also offers the best chance to treat the symptoms of the disease.
How is Alzheimer’s Disease Treated?
In the 1970’s researchers discovered that acetylcholine levels, a neurotransmitter important in the formation of memories, fell sharply in individuals with AD. Neurons in specific regions of the brain utilize acetylcholine. These areas, mainly the hippocampus and the cerebral cortex, are the parts of the brain which are most severely affected by AD. This evidence led to the idea that increasing the level of acetylcholine or hindering the breakdown of acetylcholine might be effective methods for treatment of AD. Today, the Food and Drug Administration (FDA) has approved four medications that slow or stop acetylcholinesterase, an enzyme that breaks down acetylcholine. These medications, called cholinesterase inhibitors, have been approved for the treatment of mild to moderate AD. These medications, listed below, are not able to stop the progress of AD however; they do help patients carry out daily activities.
Vitamin E is quite often prescribed as an Alzheimer’s disease treatment. These supplements may help protect the brain from free radicals, which are molecules that can damage cell structures and genetic material. Research shows that vitamin E supplements may provide some benefit to individuals with AD. A consultation with a physician should take place before an individual with AD starts on a vitamin E regimen because of the potential for an interaction with other medications the patient may be taking.
Alternative treatments include those treatments for which the safety and effectiveness is not well documented. Furthermore, the purity of these treatments and the adverse reactions one might experience are not well documented. It is important to note that these dietary supplements are not strictly regulated by the Food and Drug Administration (FDA), the governing body which approves prescription drugs.
Examples of alternative treatments:
Before a new drug can be put on the market it must be proven to be safe and effective. This is usually accomplished by clinical trials, which are research studies to investigate the new medication. The drug must then be approved by the FDA before it can be prescribed by a doctor. See this link for additional information: Clinical Trials Resource Center