Basic Alzheimer's Disease Biology
Possible Causes and Risk Factors for Development of AD
An overview of the basic biology behind Alzheimer's disease and its rising prevalence. What causes nerve cells to die and can these processes be stopped?
So what exactly sets off the cascade that ultimately leads to Alzheimer’s disease? At present no one knows. Alzheimer’s disease (AD) is the single most common cause of dementia worldwide. Some estimates have suggested that more than 5 million people in the United States currently have AD. As the baby boom generation approaches retirement age the incidence of AD appears to only be increasing.
Causes of Alzheimer’s Disease Symptoms
Alzheimer’s disease occurs when nerve cells in selected regions of the brain degenerate and subsequently die. Neurons located in brain regions specifically associated with learning and memory are particularly hard hit. As more neurons die, the brain atrophies and the symptoms worsen.
Risk Factors for Developing Alzheimer’s Disease
Unfortunately, the single largest risk factor for the development of AD is something that is unavoidable, aging. Extensive research has identified molecular factors that appear to play an important role in the development of AD, but the absolute biochemical causes are still unknown. While genetic alterations have been identified in some cases of AD, these so-called familial Alzheimer’s disease (FAD) mutations only represent 5% or less of all diagnosed cases of AD.
Pathological Hallmarks of Alzheimer’s Disease
When examined at autopsy, brains from people who had suffered from AD show very distinct pathological changes. Besides the atrophy of brain tissue owing to the loss of neurons, there are also numerous ‘amyloid plaques’ and ‘neurofibrillary tangles’. While the number of amyloid plaques present was originally thought to be an indicator of how severe the disease was at the time of death, this is no longer generally believed to be the case.
What Causes Alzheimer’s Pathology
The plaques that are found in AD brain have a very sticky, small peptide known as beta-amyloid as one of their major constituents. The beta-amyloid peptide is derived by proteolytic cleavage of a larger protein of as yet unknown function, the beta-amyloid precursor protein. The neurofibrillary tangles arise in large part because of the chemical modification (the addition of too many phosphate groups) of another brain protein known as ‘tau’. Tau normally helps to stabilize a cellular structure known as a microtubule, which is used in intracellular transport. When it is overly phosphorylated, tau likely can no longer serve this function, and intracellular transport suffers.
Why do Nerve Cells Die in AD
Research has shown that the beta-amyloid peptide is toxic to neurons, as is hyperphosphorylated tau. When these altered proteins accumulate inside of neurons they begin to exact a toll. Nerve cells are unusual in that they have very long extensions that project away from the main body of the cell and allow the nerve cells to communicate with other cells. Maintenance of these projections, known as neurites, requires a great deal of energy and biochemical building blocks. Much of these supplies are synthesized in the central body of the cell and shipped down these projections. Anything that interferes with this transport has negative consequences for the neuron.
Understanding the genetics of familial AD has shed some light on the problem. Some drug treatments have become available but they only act to slow the progression of symptoms and are not cures for the disorder. And while the overall biology of Alzheimer’s disease is startlingly complex, more is understood every day, making newer treatments likely to appear on the horizon.
