How Alzheimer's Disease Affects the Brain
Alzheimers risk factors
German neurologist Alois Alzheimer had no idea what caused the abnormal clumps and irregular knots of brain cells that he discovered in a 1906 autopsy of a woman who died after years of progressive dementia. He assumed they had caused the woman's mental deterioration, but they might also have been an effect of it.
Although science has learned a great deal more about the disease since Alzheimer's time, it's still not entirely clear whether these changes in brain tissue cause the dementia, or whether they result from some other process that causes them. However, most scientists currently believe that the clumps (called senile plaques) and knots (called neurofibrillary tangles) cause the mental deterioration. Researchers are devoting a great deal of effort to understanding how and why they develop, in order to prevent their development and return damaged brain tissue to normal.
Normally, the nerve cells in the brain are arranged in an orderly manner. In Alzheimer's disease, they become extremely disorganized and tortured-looking, and they stop functioning. As brain cells stop working, part of the brain dies, and the activities those cells control -- memory, reasoning, and ability to take care of oneself -- fade away. As more neurofibrillary tangles form, mental abilities deteriorate further, a state called progressive dementia.
Recent research has linked neurofibrillary tangles to an abnormal accumulation of a protein called tau. The link between tau and Alzheimer's remains unclear, but in recent years the protein has become the focus of a great deal of research. It is detectable in cerebrospinal fluid, and compared with unaffected individuals, people with Alzheimer's disease have noticeably elevated levels. A new test for high levels of tau in this fluid can help diagnose the disease.
Senile plaques are accumulations of cellular debris surrounding a central core of beta-amyloid peptide, a molecular fragment of a large protein found in the normal brain. Researchers first identified beta-amyloid peptide in the 1980s, some 70 years after Alzheimer discovered senile plaques. For reasons that remain unclear, beta-amyloid accumulates in the brain tissue of people with Alzheimer's and presumably plays a role in destroying it.
There are several types of beta-amyloid peptide, each differing in molecular length. The short forms tend not to form the cores of senile plaques. The one most closely linked with Alzheimer's disease is a longer form, known as beta-amyloid-42.
Like the tau protein, beta-amyloid-42 is detectable in cerebrospinal fluid. But as it forms senile plaques, its levels fall. A new test for low levels of beta-amyloid-42 can help diagnose the disease. A combination test -- simultaneously high cerebrospinal fluid levels of tau and low levels of beta-amyloid-42 -- may become a powerful tool for diagnosing Alzheimer's, but many researchers remain unconvinced.
Neurofibrillary tangles and senile plaques develop only in the parts of the brain that control memory and retention of learned information. Functions such as heart beat, breathing, and digestion remain unaffected. As a result, many people with severe Alzheimer's are otherwise healthy. Except for their minds, their other body systems may function well for their age.
Today, doctors can see the brain changes of Alzheimer's disease only on autopsy, not while people are still living. As a result, until recently, it has been difficult to diagnose Alzheimer's in the living. During the 1970s, doctors misdiagnosed many people as having Alzheimer's -- which at the time was untreatable -- when they actually had another form of dementia that might have been treatable. Today, physicians who specialize in dementing illnesses are much better at distinguishing Alzheimer's disease from the other dementias.