Stepping Closer to Develop Vaccine or Drug for Late-onset Alzheimer's

Get ready to fight Alzheimer's: New potential therapeutic approach can pave the way for developing a vaccine or drug to prevent late-onset Alzheimer's disease, reveals a new study.

Novel potential therapeutic approach brings scientists a step closer in developing a vaccine or drug to prevent late-onset Alzheimer's disease, reports a new study. The findings of the study are published in the journal eLife.

UT //Southwestern researchers have succeeded in neutralizing what they believe is a primary factor in late-onset Alzheimer's disease, opening the door to development of a drug that could be administered before age 40, and taken for life, to potentially prevent the disease in 50 to 80 percent of at-risk adults.

Alzheimer’s disease - Causes, Symptoms, Diagnosis, Stages, Types, Prevention, Prognosis & Treatment
Alzheimer's disease is a progressive neurodegenerative disease affecting memory and thinking and making the person increasingly dependent on others.

‘New study shows that scientists are moving a step forward in research efforts that could one day lead to an effective vaccine or drug to neutralize the risk of late-onset Alzheimer's disease.’
Read More..

Apolipoprotein E (ApoE) is a protein that carries fatty substances called lipids and cholesterol around the brain and plays an important role in repair mechanisms. There are three major forms of ApoE (i.e., ApoE2, ApoE3, and ApoE4); individuals who carry ApoE4 are up to 10 times more likely to develop Alzheimer's than those with ApoE2 and ApoE3 forms. ApoE4 promotes accumulation of the b-amyloid protein that causes the characteristic plaques seen in the brains of Alzheimer's patients.

UT Southwestern molecular biologist and Alzheimer's expert Dr. Joachim Herz, lead author of the study, said the goal of his team is to prevent the disease from ever manifesting. Late-onset Alzheimer's generally is diagnosed about age 65 and is the most common cause of dementia in the elderly. "If we can negate the ApoE4 process early, we may be able to prevent late-onset Alzheimer's altogether for many people so that they will never get sick," Dr. Herz said.

ApoE4 has been shown to suppress and trap synaptic receptors within intracellular vesicles. However, how the ApoE4 gets trapped has remained a mystery until now. According to Dr. Herz, ApoE4 is the root cause of a "traffic jam" inside the cells that take up ApoE4, and this is associated with reduced recycling of intracellular endosomal transport vesicles.

Genetics of Alzheimer’s disease
There are numerous genes that have been discovered that are associated with Alzheimer’s disease and indicate increased risk, aiding genetic counseling and better care.

UTSW researchers found that lowering the pH of these endosomes, i.e., by making them more acidic, cleared the traffic jam: The scientists were able to completely reverse the ApoE4-induced recycling block in mice through pharmacological and genetic inhibition of the NHE6 protein, which acts to make the endosomal vesicles less acidic.

These findings suggest a novel potential therapeutic approach for the prevention of late-onset Alzheimer's disease, Dr. Herz said. The vesicle traffic jam due to the selective loss of solubility of ApoE4 likely is the earliest mechanism at which the protein negatively affects nerve cells, Dr. Herz said.

Diet and Alzheimer's Disease
Alzheimer's begins with forgetfulness, but over time affects speech and coordination along with drastic behavioral changes. The right diet may lower your risk by 40%. So isn't a diet change worth it?

Most Alzheimer's research has focused on halting the formation of amyloid and tau protein aggregates once they exist in the brain and degeneration has already begun. "Our approach in this study was to stop the overall degeneration process earlier; that is, before the formation of these aggregates," Dr. Herz said.

The next step is to develop tailor-made, small molecule inhibitors that can enter the brain efficiently and selectively block NHE6, he added.

World Alzheimer�s Day
World Alzheimer’s Day is observed annually on 21st September around the world with the primary aim to raise awareness and challenge the common stigma that surrounds Alzheimer’s related dementia.

"The beauty of NHE inhibitors is that these are small molecules that can be produced inexpensively and thus made widely available, in contrast to the more elaborate antibody-based therapies that are currently being evaluated in clinical trials. A simple pill could someday neutralize the risk of late-onset Alzheimer's disease just as readily available statins are able to reduce the risk of cardiovascular disease," Dr. Herz said.

Source-Eurekalert