Alzheimer's disease or AD, the most common cause of dementia in the elderly, is a heterogeneous group of neurodegenerative disorders. When first reported by Alois Alzheimer in 1907, the incidence of AD was low, probably because few individuals lived long enough to develop the disease. But, astonishing increases in life expectancy over the last 100 years have led to a “longevity revolution.” Between the year 2000 and 2030, the number of people over age 65 is expected to double, and by 2050, there may be five times the number of people over age 85 than there were in 2000
One consequence of the longevity revolution is an increase in the number of people with AD. In 2008, there were about 5.5 million Americans with AD, and this number is expected to soar to about 13 million by 2050 if nothing is done to delay or prevent the onset of the disease.
The cost to Medicare for treating AD patients is also expected to explode, from about $62 billion in 2000 to around $1 trillion by 2050.
The major symptom of AD is progressive forgetfulness leading to dementia, but other cognitive functions (language, orientation in time and place, etc.) also deteriorate, and disease may extend over 5-15 years.
Why These Symptoms Occur
Studies of the AD brain at autopsy show dramatic changes in brain structures that are thought to arise from the death of brain cells called neurons. Interestingly, examination of the brains of people who show no signs of dementia also often reveal loss of neurons, but the loss in people with AD generally exceeds that seen during normal aging. Also, there are specific areas of the brain that appear to be more affected in people with AD than in normal aging, particularly an area called the hippocampus,. Since the hippocampus is implicated in the formation of memory, this could explain the intellectual deficits that are the hallmark of AD.
Most people (about 90%) with AD have a form called sporadic AD, but 10% have what is called Familial AD (FAD), which means that it is inherited, or “runs in the family.” About half of those with FAD have been shown to have disease causing mutations in genes on chromosome 14 (Presenilin 1 or PS1), chromosome 1 (Presenilin 2 or PS2), and chromosome 21 β precursor protein or Aβ , while chromosome 19 harbors a risk factor gene (apolipoprotein E) for AD. It is not clear how these mutations or trisomy 21 in Down syndrome (DS) lead to AD.
Five drugs have been approved for treating the cognitive and memory symptoms associated with AD and three other drugs are approved for other symptoms, such as psychosis, depression and anxiety. None of these drugs are thought to be disease modifying, in that they do not slow or delay onset of the disease. Many other drugs are in various stages of development. For more information on these drugs, visit the AlzForum website.
Finding a Cure
Examination of the tissue from AD brains has revealed characteristics that help explain the disease process. The two hallmark brain lesions of AD are commonly known as plaques and tangles. Plaques accumulate around brain cells and are composed of aggregates of a protein called β-amyloid; while neurofibrillary tangles (NFTs) are composed of a protein called tau and are found inside of the neurons. These plaques and tangles accumulate most prominently areas of the brain called the neocortical and limbic brain regions. In fact, diagnosis of definite AD in a demented patient requires detection of abundant plaques and NFTs in the postmortem brain or a brain biopsy. Scientists at CNDR and elsewhere are attempting to identify precisely how these plaques and tangles form and whether interrupting this process would prevent neurodegeneration and dementia.