People with AD gradually suffer memory loss and a decline in thinking abilities, as well as major personality changes. These losses in cognitive function are accompanied by changes in the brain, including the build-up of amyloid plaques and tau-containing neurofibrillary tangles, which result in the death of brain cells and the breakdown of the connections between them.
Amyloid plaques and neurofibrillary tangles are the primary hallmarks of Alzheimer’s disease. Plaques are dense deposits of protein and cellular material outside and around the brain’s nerve cells. Tangles are twisted fibers that build up inside the nerve cells. Scientists have known about plaques and tangles since 1906, when a German physician, Dr. Alois Alzheimer, first identified them in the brain of woman who had died after suffering paranoid delusions and psychosis. Intensive research efforts of the last two decades have revealed much about their composition, how they form, and their possible roles in the development of Alzheimer’s disease. The deposition of amyloid in the form of plaques is thought by many scientists to trigger the cascade of events leading to Alzheimer’s pathology. Amyloid now is believed to be a critical target for eventual treatment. The best evidence that amyloid causes the disease comes from the genetic studies in which mutations of APP, PS1, PS2 and APOE e4 (the genes so far identified as causing some cases of Alzheimer’s) all facilitate amyloid accumulation.
As the disease progresses, nerve cells in several brain areas shrink and die, including cells that normally produce critical neurotransmitters, the chemical messengers that relay brain signals from one nerve cell (neuron) to another. Acetylcholine is a neurotransmitter that is deficient in people with Alzheimer’s. As nerve cells continue to die, the brain itself shrinks and the wrinkles along its surface become smoother.