There Is Now Potential for an Alzheimer's Cure

There Is Now Potential for an Alzheimer's Cure

Researchers and doctors have now come to recognize that Alzheimer's disease (AD) is a major public health crisis that is rapidly expanding in scope. Alzheimer's disease diagnoses have increased in tandem with the percentage of the U.S. population over 65 years old.

Alzheimer's disease is the most common kind of dementia in those over the age of 65, with an estimated 10% risk for those over the age of 65 and a 50% risk for those over the age of 85. In addition to memory loss, other significant problems can be caused by Alzheimer's disease, such as personality shifts, confusion, trouble with speech and comprehension, and an inability to carry out regular bodily movements.

Most people with Alzheimer's need a lot of care, and that ends up costing the world close to $100 billion a year in medical bills and lost productivity. Alzheimer's disease will have an even greater impact on society as the population ages, says Christian Fritze, Ph.D., director of the Antibody Products Division at Covance Research Products. Disease prevalence and detrimental consequences for the patient are noteworthy in their own right. The far-reaching implications for families, caregiving networks, and the health care economy are also becoming more and more apparent. The research and drug development community is more motivated to make strides toward effective treatments.

An Emerging Agreement

But there is reason for optimism, thanks to recent advances in medical science. In the last two years, scientists have come closer to agreeing on what causes Alzheimer's disease, which has helped them narrow in on potential new treatments.

An updated version of the "amyloid cascade hypothesis" centers on amyloid beta oligomers. The widespread adoption of this new finding marks a significant turning point in the battle against Alzheimer's disease. The progenitors of amyloid plaques have been the subject of a decades-long search for the cause of Alzheimer's disease, as stated by Dr. Fritze. Amyloid precursor protein (APP) variations, Tau isoforms, and secretase components all contribute to neuronal cytotoxicity and, ultimately, brain dysfunction.

In the brain, amyloid beta peptide forms sticky protein deposits called amyloid plaques. Since its discovery in 1907, researchers have linked this plaque to Alzheimer's disease. Despite the obvious link, researchers still lacked a clear understanding of what precipitated the start of Alzheimer's disease.

Over the past decade, researchers have focused extensively on the theory that amyloid beta buildup in the brain is the primary etiology of Alzheimer's disease. This was the most popular theory for explaining Alzheimer's disease, although it had major flaws. The accumulation of amyloid beta peptides was not always correlated with the severity of Alzheimer's symptoms, which was the most glaring flaw in the idea.

Researchers in 1998 and 2002 claimed that precursors of amyloid beta plaques created by smaller aggregates of amyloid beta were neurotoxic and thus the origin of Alzheimer's disease. There is now agreement among those who study Alzheimer's, thanks to the introduction of these novel ideas.

This fresh impetus should serve as a reminder to those working to find a cure for Alzheimer's that there is still much work to be done. Dr. Fritze states that in order to follow these components and quantify the presence of monomeric, oligomeric, and fibrillar amyloid forms present in the evolution of Alzheimer's disease, the AD field requires advanced, very sensitive research methods.

Injection of antibodies

New therapeutic alternatives may soon be available, according to two studies published in October 2004. Amyloid beta (Aβ) antibodies have been tried twice before in attempts to treat Alzheimer's disease, but in these experiments, a different approach was taken. Though unsuccessful, prior attempts provided significant information and suggested new directions for Alzheimer's research.

Researchers introduced bits of the beta-amyloid protein that makes up amyloid plaque into mice in the first of two earlier attempts to elicit an immunological (antibody) reaction against amyloid. The initial findings were promising. Antibodies against Aβ were generated in response to the injected antigen, and the disease's progression was halted as a result. When tested on humans, however, the technique was stopped because it caused meningoencephalitis (an inflammation of the tissue around the brain) in certain individuals.

In the second effort, mice were treated with antibodies against amyloid beta (not amyloid protein), but the high antibody dosages needed to be effective caused bleeding and inflammation.

Some Optimism

However, there is currently renewed optimism for the therapeutic potential of antibodies in the treatment of Alzheimer's disease. Researchers at NCGG (National Center for Geometric Genomics) and the Center for Neurological Diseases (Brigham and Women's Hospital, Harvard Medical School) revised the original method in the first of two new studies published in October. The researchers reasoned that autoimmune T-cell activation was to blame for the meningoenchaphalitis seen by some patients, and so they set out to create a vaccination that would reduce T-cell activation while maintaining the development of Aß antibodies. They did this by developing an oral vaccination that uses Aß DNA coupled to an adeno-associated viral vector to reduce T-cell activation. The risk of meningoencephalitis was considerably reduced as a result of the decrease in Aß levels in the mouse brains without an accompanying increase in T-cell activation.

The second recent study had the opposite goal, and it was successful in making the passive immunity strategy safer. To do this, they shifted where the Aß antibodies were being introduced. Instead of putting the antibodies into the mice's bodies, as was done in the past, the antibodies were administered into the mice's brains. Injecting the antibodies directly into the brain reduced the required dosage and the risk of adverse reactions.

Potentially game-changing in the annals of Alzheimer's treatment are the findings of the aforementioned trials, as well as the prospect of more enhanced immunization techniques.