Researchers at North Carolina Central University (NCCU) are engaged in two areas of research connected to Alzheimer’s Disease.
Alzheimer’s Disease is the most common form of dementia, accounting for about 80% of all dementia cases. It is the sixth leading cause of death among U.S. adults, according to the U.S. Center for Disease Control and Prevention, and the 5th leading cause of death for adults aged 65 and older. There is no cure for the disease.
Researchers at the NCCU Biomanufacturing Research Institute & Technology Enterprise (BRITE) have focused their strategies on how to slow or halt the progression of Alzheimer's rather than cure it, as many drugs developed to treat the illness failed in clinical trials.
Alzheimer's disease is marked by the accumulation of two proteins called Amyloid-beta and Tau in the brain. Amyloid-beta forms sticky clumps (plaques), while Tau creates tangled (knots). These clumps and tangles damage brain cells or neurons, leading to memory loss and other symptoms. Some medicines can slow the buildup and even clear these proteins from the brain, but no drug has been able to stop or reverse the damage.
“It is primarily an age-related disease,” said Gordon Ibeanu, Ph.D., chair of the department of pharmaceutical sciences and the interim director of BRITE.
Age is the best-known risk factor, although genetics, family history, medical conditions and lifestyle habits could factor in. Alzheimer’s primarily impacts people who are in their 60s or older.
“If we can slow down how fast it progresses by 10 to 20 years, Alzheimer’s will be more of a chronic disorder rather than a life-threatening disease,” Ibeanu said. “That has been the research objective of my group.”
More specifically, Ibeanu’s group of researchers is using a two-prong approach focused on searching for chemical molecules that will protect brain cells from death (neuroprotection) caused by Amyloid Beta, as well as to slow down the aging process.
The team is conducting research on a family of enzymes called Sirtuins, which help to regulate aging. They hope that by activating SIRT1, a member of this enzyme family, they can slow the aging process which may reduce or avoid the buildup of plaques in the brain.
“We are looking for molecules that can trigger this enzyme,” said Adekunle Rowaiye, DVM, Ph.D., a research scholar at BRITE and adjunct faculty in the department of pharmaceutical sciences.
Rowaiye uses artificial intelligence to find molecules that could trigger SIRT1. Those ranked most likely to succeed then go to the laboratory to be tested on cell models.
“It reduces time, cost and labor instead of randomly testing chemical compounds in the laboratory,” Rowaiye said.
Early Detection
Concurrently, researchers are also trying to detect Alzheimer’s Disease early so any treatment can also be applied early.
“It takes ten to 20 years to develop Alzheimer’s,” said Ling Wu, MD, Ph.D., a research assistant professor in BRITE “We want to detect it as early as possible.”
Bin Xu agrees.
“We want to diagnose early so we can treat early,” said Bin Xu, Ph.D., an associate professor in BRITE.
Xu seeks biological markers (biomarkers) that indicate the presence of tau proteins which form tangles.
Tau, a naturally occurring protein, clumps together in the brains of people with Alzheimer’s, forming ‘tangles.’ That change is toxic to the brain cells and disrupts the brain’s ability to transmit electrical signals.
Ideally the tau proteins could be detected with a blood test, although due to the blood/brain barrier, brain proteins are usually found in very low amounts in blood.
Another more invasive possibility is examining cerebral spinal fluid (CSF).
In addition to state funding from BRITE, Xu obtained a major research grant from the National Institute of Health (NIH) and North Carolina Biotechnology Center. Some of these funds were used to purchase instruments that allows Xu and his group to develop new technologies that are extremely sensitive in detecting very low levels of biological molecules in blood or CSF, said Xu.
Typically, one of the first symptoms of Alzheimer’s Disease is memory loss, according to the NIH. A decline in other aspects of thinking such as finding the right words or impaired reasoning may also signal early stages of Alzheimer’s.
“We don’t know what causes Alzheimer’s,” Ibeanu said. “It continues to be a puzzle for researchers working in this field.”
The incidence of Alzheimer’s disease is higher in African Americans. While reasons are unclear, Ibeanu said a genetic component and less access to health care might be factors.
Ibeanu notes that African Americans have been underrepresented in studies of Alzheimer’s, including clinical trials for potential drugs.
Alzheimer’s Disease is projected to increase in the U.S. as the population ages.
