Alzheimer's Disease

One of the most frightening and devastating of all neurological disorders is the dementia that can occur in the elderly. The most common form of this illness is Alzheimer’s disease.

Rare before age 60 but increasingly prevalent in each decade thereafter, Alzheimer’s affects 5 percent of Americans age 65 to 74 and nearly half of those age 85 and older. As many as 5.3 million Americans have Alzheimer’s. The disease is predicted to affect approximately 14 million individuals in the United States by the year 2050.

The earliest symptoms of Alzheimer’s include forgetfulness; disorientation as to time or place; and difficulty with concentration, calculation, language, and judgment. As the disease progresses, some patients have severe behavioral disturbances and may even become psychotic. In the final stages, the affected individual is incapable of self-care and becomes bedridden. Patients usually die from pneumonia or some other complication of immobility. Alzheimer’s disease is the seventh leading cause of death in the United States and the fifth leading cause of death for Americans aged 65 and older.

In the earliest stages, the clinical diagnosis of possible or probable Alzheimer’s can be made with greater than 80 percent accuracy. As the course of the disease progresses, the accuracy of diagnosis at Alzheimer’s research centers exceeds 90 percent. The diagnosis depends on medical history, physical and neurological examinations, psychological testing, laboratory tests, and brain imaging studies. New brain imaging strategies now allow doctors to visualize Alzheimer’s neuropathology during life. At present, however, the final, definitive diagnosis is usually only reached after examination of brain tissue obtained at autopsy.

The search for Alzheimer’s causes

The causes of Alzheimer’s are not yet fully understood, but great progress has been made through the study of genetics, biochemistry, and cell biology, as well as through the use of experimental treatments. Neuroscientists do know that there is wide spread loss of brain cells as well as reductions in markers for many neurotransmitters that allow cells to communicate with one another. These include acetylcholine, somatostatin, monoamines, and glutamate. Damage to these neural systems, which are critical for attention, memory, learning, and higher cognitive abilities, is believed to cause the clinical symptoms.

Microscopic examination of brain tissue from people who died from Alzheimer’s shows abnormal fibrillar accumulations of a small peptide, termed beta amyloid. These aggregates are called neuritic plaques and they are found in the spaces between cells rather than in the cells themselves. Another abnormal protein aggregate, called a neurofibrillary tangle, also accumulates in the Alzheimer's disease brain. These tangles consist primarily of a modified form of the protein tau. In all forms of Alzheimer’s, plaques and tangles mostly develop in brain regions important for memory and intellectual functions. New brain imaging strategies that may one day be used for diagnosis use a mildly radioactive chemical marker that shows amyloid plaques and tau tangles in living people. 

Early-onset Alzheimer’s disease is usually caused by rare, dominantly inherited disease genes. Scientists now recognize three such Alzheimer’s disease-associated mutations. They include the gene encoding the amyloid precursor protein (APP) on chromosome 21 as well as mutations in the closely related presenilin 1 and 2 genes. Apolipoprotein E (apoE), while not formally a disease causing gene, influences susceptibility for Alzheimer’s later in life. APOE is a protein whose function is to carry water insoluble lipids (fat) in blood and in brain. The variant known as APOE epsilon 4 is associated with a 5-10 fold enhanced risk of Alzheimer's.