Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting over 5 million people in the USA today. The first AD symptoms occur during the stage known as mild cognitive impairment (MCI), and usually begin after age 55. About 10% of AD patients have an earlier onset, in which the first symptoms begin between ages 35 and 55.

Neuropathological Hallmarks of AD
The two main neuropathological hallmarks in the AD brain are amyloid plaques and neurofibrillary tangles.

• Amyloid plaques build up between nerve cells. They contain insoluble fragments of protein called beta-amyloid, which are toxic, and literally short-circuit the brain's ability to communicate between nerve cells.
• Neurofibrillary tangles form inside of nerve cells. A nerve cell is composed of a tubular skeleton made up of tau proteins. In AD, excessive calcium entry into neurons causes too many phosphate ions to bind to the tau proteins, which twists the tubular skeleton into a dense collection of spiral staircases that disrupt neuron function. Eventually these spiral staircases become all tangled up to form a neurofibrillary tangle, at which point the neuron has died.

The Earliest Symptom of AD
The earliest symptom of AD is short-term memory loss, which may express itself as anxiety, irritability, depression, withdrawal, loss of confidence, forgetfulness, repeating questions, a decline in work performance, or difficulty with highly complex skills. Short-term memory loss is often confused with the decline in working memory that occurs with normal aging (learn more).

Importantly, short-term and working memory loss can be readily distinguished with an appropriate memory test. Because detection of the earliest changes in AD is the key to halting or substantially delaying its progression, it is critical to distinguish memory decline due to normal aging from that due to AD and related disorders. Such early detection delays AD so effectively that it usually eliminates being institutionalized plus preserves your ability to enjoy your life's pursuits.

Genetics of AD
About 10% of AD cases are early-onset, familial or hereditary AD and affect people in their 30s, 40s and 50s. Among persons with later onset AD, in which the mild cognitive impairment (MCI) stage begins after age 55 years old, about 40% have a hereditary form due to the epsilon 4 gene, which produces apolipoprotein E (APOE-e4). Whether you have the APOE-e4 gene or not can be determined by a simple blood test. If you have the APOE-e4 gene, this does not mean that you will develop AD, but it does indicate that you have a higher risk for developing AD. Since this risk may be reduced through the proper preventive treatment strategy, it may be worth knowing whether you have the APOE-e4 gene, but that is an individual's decision.

Cost of AD
AD is one of the four most costly diseases of aging. AD costs $100 billion annually in the USA, with each affected family spending an average of $25,000 per year toward a total cost of $200,000 per AD patient. These figures do not include costs of unpaid care giving by family members or caregivers. Since most patients with AD are currently detected four or more years after the first symptoms appear (halfway through the 8-year course of the disease), detecting and treating AD earlier would reduce the cost of care by an estmated $100,000 to $200,000.

History of AD
In 1906, Alois Alzheimer, a psychiatrist and pathologist in Germany reported the story of a 55-year old female who died after several years of progressive dementia (Alzheimer, A., 1907, 1995). In her brain he had found both neuritic plaques and neurofibrillary tangles. This was the first report of Alzheimer's disease (AD). In 1900, however, the average life expectancy was about 40 years old, so AD occurred rarely. Since then, as life expectancy has increased to over 70 years of age in developed countries throughout the world, the prevalence of AD has necessarily increased so that it is now a major economic healthcare problem and is the most common neuronal degenerative disease of aging.