The Disease

 

Alzheimer’s disease is a devastating neurodegenerative disease of the central nervous system for which there is no disease-modifying treatment. Alzheimer’s disease is responsible for 60-80% of all cases of dementia and progressively destroys the cognitive abilities of its victims. The disease is named after Dr. Alois Alzheimer who, in 1906, first described brain shrinkage and plaques and tangles in the brain of a woman who died with an unexplained mental illness that featured memory loss and behavioral instability.
Today, the scientific community suggests that two proteins are implicated in the pathology of Alzheimer’s disease: Amyloid beta (Abeta) and Tau protein. Abeta is a fragment of a larger, membrane-bound protein whose normal function is believed to be in the forming and dissolving of connections between brain cells that are needed for nerve cell communication. According to the Amyloid Cascade Hypothesis, these monomeric fragments of Abeta misfold in a chain reaction, then aggregate to form multi-unit oligomers which then form fibrils that are deposited in the brain as the amyloid plaques that were first described by Alois Alzheimer.

The other protein implicated in the pathology of Alzheimer’s disease is Tau protein whose normal function is as part of the internal structural support of cell. This protein, too, misfolds in a spreading chain reaction and it becomes hyperphosphorylated in its pathological form. Misfolded, hyperphosphorylated aggregates of Tau protein form characteristic Tau tangles and structures known as paired helical filaments that are found in the brains of Alzheimer’s patients. There is a hypothesis that misfolded Abeta aggregation triggers Tau protein misfolding and that Alzheimer’s disease is an Abeta-mediated tauopathy. Although the underlying cause of Alzheimer’s disease remains unknown, Abeta aggregates and Tau tangles cause brain cell death and are therefore the targets of many drugs in development. Other approaches target the oxidative damage and inflammation that are also seen.


The symptoms of Alzheimer’s disease usually develop in three general stages:

Mild Alzheimer´s Disease
People are often diagnosed with mild Alzheimer´s disease due to memory loss and changes in other cognitive abilities. Problems can include getting lost, having trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, poor judgment, and mood and personality changes.

Moderate Alzheimer´s Disease
In this stage, damage occurs in areas of the brain that control language, reasoning, sensory processing, and conscious thought. Memory loss and confusion increase, and people begin to have problems recognizing family and friends. They may be unable to learn new things, carry out tasks that involve multiple steps (such as getting dressed), or cope with new situations. They may have hallucinations, delusions, and paranoia, and may behave impulsively.

Severe Alzheimer´s Disease
By the final stage, plaques and tangles have spread throughout the brain and brain tissue has shrunk significantly. People with severe Alzheimer´s Disease cannot communicate and are completely dependent on others for their care. Near the end, the person may be in bed most or all of the time as the body shuts down.

 

Diagnosis

Currently there is no efficient diagnostic test that detects the early onset of Alzheimer´s disease. The disease can be definitively diagnosed only after death upon autopsy.
Current test methodologies include cognitive tests as well as imaging studies, blood tests and tests on cerebral spinal fluid. A number of biomarkers are being investigated with the hope of developing a blood test that can identify the disease at a very early stage.
Early diagnosis is becoming increasingly important as most drugs in development focus on treating early stage disease in order to delay progression and preserve the maximum amount of cognitive ability. The availability of disease-modifying therapeutics will further drive the development of accurate diagnostic tests.