Alzheimer's Disease: A Brief History and Avenues for Current Research

Author:  Reger Beth
Institution:  Neurobiology
Date:  September 2005

All too frequently, people are discovering that a grandparent, parent, elderly relative, or friend can no longer remember names or faces, recognize common objects, or talk in coherent sentences. This person may be suffering from Alzheimer's disease (AD). Alzheimer's disease is a growing medical and social concern. Zaven Khachaturian and Teresa Radebaugh, in their 1996 book Alzheimer's disease: Cause(s), Diagnosis, Treatment, and Care, state that AD strikes more than 4 million people in the United States alone and affects millions more who suffer from watching a loved one afflicted with the disease. In the last 30 years, AD has become a hot topic in both the medical and non-medical communities.

Khachaturian and Radebaugh describe AD as a "degenerative disorder that attacks the brain and leads to dementia." The brain's cognitive centers are affected, causing memory loss and the inability to understand situations or even questions or statements. As the disease progresses, social interactions diminish, and the afflicted person loses the ability to care for him or herself.

The duration of AD, from onset to death, ranges from two to 20 years. Symptoms of AD will often become noticeable between the ages of 65 and 85, becoming more prevalent as the person grows older and the disease progresses. Although rare, AD can manifest as early as age 45, and is termed "early onset" Alzheimer's disease when it occurs before 65.

Discovery and diagnosis

AD was discovered in 1907 by Alois Alzheimer, but was not considered a major disease or disorder until the 1970s. Alzheimer documented a case of a woman in her fifties who exhibited severe cognitive disorders pertaining to memory, language, and social interaction, according to Khachaturian and Radebaugh.

After the patient's death, Alzheimer performed an autopsy on her brain, using a silver staining technique that allowed him to visualize the presence of neurons. In the process he found unusual formations, now known as senile plaques and neurofibrillary tangles. Alzheimer hypothesized that these lesions might be the cause or effect of the as yet to be named Alzheimer's disease, or possibly a combination of the two. The disorder was later named for Alzheimer as more people were found to have the symptoms associated with his findings.

Before Alzheimer's 1907 discovery, both scientists and the non-science community viewed dementia as a "natural" progression of age, and "senility was accepted as a part of aging," according to Natalie Whaley in her honors thesis on the social history of Alzheimer's disease.

Additionally, AD was not differentiated from other types of age-induced dementia or senility. Alzheimer's disease did not suddenly "appear" in 1907, rather it was then that the disease was first recognized and named.

Even with Alzheimer's discovery, however, the disease was not one that was accepted as, well, a "disease." Senility and dementia were still considered part of the aging process. Whaley states that AD did not become a common term, or even a large concern, until neurological research exploded in the late 1970s.

With the creation of the Alzheimer's Association in 1985, AD has gradually been accepted as a disorder and less as a natural function of aging, although age is still a risk factor for AD, Whaley says.

A biological basis for AD?

Scientists now strongly believe there is a biological basis for AD. Research has shown that the presence of plaques and tangles lead to the onset and severity of AD, and genetics may play a role as well, albeit a much smaller role than plaques or tangles. Senile plaques result from an aggregation of the protein amyloid beta (Ab) outside the cell membrane and are therefore known as extracellular deposits. Ab is a naturally occurring neuronal substance, and only becomes a problem when the body ceases to metabolize and remove the excess. If the protein is not removed, it aggregates around the neurons and prevents transmission of electrical signals from one neuron to the next.

Tangles also block the passage of information between neurons. Neurofibrillary tangles, composed of a protein known as tau, form within the neurons themselves and are considered intracellular lesions, as they cause the death of surrounding cells. In effect, AD is not a disease of the neurons themselves, but a disease of the communication between the neurons.

Difficulties and progress in research

Research on AD is difficult for several reasons. First, AD develops slowly and is difficult to diagnose. Cognitive deficits vary between patients, and correlate to the amount of education and social interaction the patient has experienced in his or her lifetime. Poor performance on an IQ test, for example, may reflect a lower level of education, and not Alzheimer's disease. Thus it is necessary to have a well-documented patient history (mental as well as physical) and this is not always available.

Secondly, it is difficult to obtain accurate histochemical information, which would require observation of brain samples during different phases of the disease. However, neurological biopsies are ethically questionable, and brain dissection can only be performed post-mortem.

Due to these problems, researchers have focused on treating the symptoms of AD, in an attempt to delay the progression of the disease. According to Roger Knowles, professor of neurobiology at Drew University, current AD research is focusing on presenilins and amyloid precursor protein (APP), both of which contribute to the formation of senile plaques. Presenilins and APP are particularly associated with early onset AD.

Scientists are utilizing transgenic animal models to experiment with large quantities of presenilins and APP, and have discovered that the animals, in turn, exhibit severe plaque production.

Scientists are attempting to discover ways to clear the plaques, in hopes of restoring neuronal function or delaying the progression of the disease. They are currently working with two methods: developing drugs that encourage the immune system to attack the plaques; and designing peptides that will interfere with the b-sheet conformation of the Ab protein and leave the protein unable to aggregate in the form of plaques.

Researchers also continue to investigate the cholinergic hypothesis of AD. Some studies have shown AD patients exhibit low levels of the neurotransmitter acetylcholine, which is involved in memory processes. Scientists believed that increasing levels of choline (which is involved in the production of acetylcholine) in the brain might slow cognitive decline. However, according to Martina Habeck, in her 2002 review of current Alzheimer's research, choline treatments have not proven as fruitful as was once hoped since acetylcholine is just one of many factors associated with AD.

At present, there is no known cure for AD. Current research focuses on a better understanding of the disease and its causes. Although a cure for this devastating disease may not be realized for quite some time, it is probable that scientists will discover ways to slow the progression of the disease, and therefore reduce the suffering of so many people worldwide.

Suggested Reading

Habeck, M. "New Insights into Alzheimer's Disease." Drug Discovery Today, 2002, 7 (8): 441-442.

Holstein, M. "Alzheimer's Disease and Senile Dementia, 1885-1920: An Interpretive History of Disease Negot! iation." Journal of Aging Studies. 1996, 11 (1): 1-13.

Khachaturian, Z.S., Radebaugh, T.S., Alzheimer's Disease: Cause(s), Diagnosis, Treatment, and Care. New York: CRC Press, 1996.

Maccioni, R.B., Mu–oz, J.P., Barbeito, L. "The Molecular Bases of Alzheimer's Disease and Other Neurodegenerative Disorders." Archives of Medical Research. 2001, 32 (5): 367-381.

Toreilles, F., Touchon, J., "Pathogenic Theories and Intrathecal Analysis of the Sporadic form of Alzheimer's Disease." Progress in Neurobiology. 2002, 66: 191-203.

Whaley, Natalie S. "Senility, Confusion, Debate, Fear: Conceptualizing Alzheimer's Disease and the History of Senile Dementia." Thesis. Drew University, Madison, NJ, 2002.

Usita, P.M., Hyman, I.E. Jr., Herman, K.C. "Narrative Intentions: Listening to Life Stories in Alzheimer's Disease." Journal of Aging Studies. 1998, 12 (2): 185-197.