Alzheimer's Disease affects 12 million people worldwide with the numbers expected to rise if a cure or preventative measures are not found. Characteristics of Alzheimer's Disease include pre-senile dementia and relentless irreversible brain degeneration leading to memory loss, impaired judgment, difficulty expressing oneself through speech, the inability to work and death. The mental degeneration characteristic of Alzheimer's is caused by a loss of nerve cells in the brain, particularly in areas associated with memory and learning.

Alzheimer's Disease has become the fourth leading cause of death in people over the age of 75 in the United States and Congress has classified the treatment of this disease as a major national priority.

The cost of treatment alone can increase the patient's and family's financial and emotional burden dramatically. For one patient to receive ARICEPT , the leading Alzheimer's treatment, for one year, the approximate cost is $1,825 ( $5 a day for 365 days). The total per patient cost for treatment is approximately $170,000 per year. This cost becomes astronomical as you multiply that number by the estimated 5 million reported cases of Alzheimer's Disease in the year 2000.

Current clinical diagnostic procedures are about 80% accurate but no conclusive diagnosis can be made before the patient dies. 

The onset of Alzheimer's Disease, like many other forms of dementia, also affects the levels of a certain neurotransmitter in the brain. Neurotransmitters are chemical substances that act as messengers relaying impulses between nerve cells. These neurotransmitters operate in the synapses, the space between the transmitting axons and the receiving dendrites of nerve cells.

A shortage of the neurotransmitter acetylcholine can lead to memory loss or impairment of other cognitive functions. Production of acetylcholine is greatly diminished in the brain of Alzheimer's Disease patients due to the death of nerve cells.

Since 1906, researchers noted abnormalities called plaques and tangles in samples of brain tissues taken at autopsy from persons who were thought to have died of AD. The presence of these plaques and tangles ultimately became the gold standard for a positive post-mortem diagnosis of AD. In 1978, a team of neurological researchers led by Blessed and Tomlinson reviewed a large sample of autopsied brains. They published two articles concluding that all AD patients exhibited numerous amyloid plaques, containing degenerating nerve endings in amounts far exceeding what one observed in normal aging brain tissue.

Amyloid is a generic name for protein fragments that aggregate (collect or clump together) in a specific way to form insoluble deposits referred to as plaques that build up outside of neurons.

Tangles are insoluble twisted protein fibers that build-up inside neurons. Much progress has been made in determining the makeup of amyloid plaques and neurofibrillary tangles and in proposing mechanisms that account for their build-up in the brains of people with AD. Amyloid plaques develop first in the area of the brain used for memory and other cognitive functions.

The plaques are thought to be a key element of the disease and are composed primarily of the toxic form of a naturally occurring protein called beta-amyloid , which is produced in excessive quantities in the Alzheimer brain. The beta-amyloid protein undergoes a change in structure and accumulates as insoluble fibril deposits in and around nerve cells and on the walls of blood vessels in the brain of the afflicted individual. Keeping the plaques from forming or dissolving existing plaques with amyloid is at the cutting edge of the war on Alzheimer's Disease.

The principal component of amyloid plaques is a peptide designated as beta-amyloid, A. Beta-amyloid is a small fragment of a much larger protein called amyloid precursor protein (APP), which is a member of a larger family of proteins associated with cell membranes.

The cell membrane encloses the cell and acts as a barrier to selectively control which substances can go in and out of the cell. During normal metabolism, APP is degraded by proteases to several fragments, one of which is A. Beta-amyloid is produced only when two specific proteolytic cleavages occur within APP.

Beta-amyloid can be formed in two different lengths: 40 amino acids or 42 amino acids. The shorter form, A₄₀ is more soluble and aggregates slowly. The slightly longer, sticky form, A₄₂ , rapidly forms insoluble aggregates and appears to play a critical role in the initial build-up of plaques and in the onset of AD. In the later stages of AD, A₄₂ aggregates into long beta-amyloid filaments outside the cell and, along with fragments of dead and dying neurites (nerve endings), form the dense, insoluble amyloid plaques that are the hallmark for identifying AD in brain tissue.

The most favored theory of the initiation of AD is that A42 initiates the chronic and unremitting AD process by aggregating to form insoluble amyloid plaques. A42 is an early factor in the slow, multistep process that ultimately leads to nerve cell damage and death of the brain. The accumulation of plaques seems to occur because the body cannot properly dispose of or recycle this peptide.

Understanding the roles that A and APP play in nerve cell damage in the Alzheimer’s brain is the focus of significant research efforts around the world to develop strategies that block A generation or enhance the clearance of A from the brain.

Return to Targeted Diseases