New research suggests a different therapeutic approach may be helpful in reducing the effects of Alzheimer’s disease. In the study, University of Kentucky investigators discovered an antibody that targets neuro-inflammation may reduce the development of amyloid plaques and neurofibrillary tangles and improve cognition.
Alzheimer’s disease affects more than 3 million Americans each year. Most people with Alzheimer’s develop what is called the late-onset variety in which symptoms first appear in their mid-60s. However, early-onset Alzheimer’s can begin with symptoms between a person’s 30s and mid-60s.
The first symptoms of Alzheimer’s vary from person to person. Dementia is the term applied to a group of symptoms that negatively impact memory, but Alzheimer’s is a progressive disease of the brain that slowly causes impairment in memory and cognitive function.
The new findings and approach result from an explosion of genetic data suggesting the risk for sporadic Alzheimer’s disease is driven by a variety of factors including neuroinflammation, membrane turnover and storage, and lipid metabolism.
Investigators said current therapeutic approaches for Alzheimer’s focus on the major pathological hallmarks of the disease, the plaques and tangles. Indeed, these factors are the pathological requirements for a diagnosis of Alzheimer’s.
In this study, published in the Journal of Neuroinflammation, scientists focused on triggering a receptor expressed on myeloid cell-2 (TREM2) to reduce or prevent the development of the amyloid plaques and neurofibrillary tangles. They believe creating an antibody could activate the cell receptor an opposite action that occurs when a mutation suppress the cell resulting in Alzheimer’s.
“TREM2 was identified several years ago as a gene that, when there’s a mutation, significantly increases risk of Alzheimer’s disease. The field thinks that this mutation reduces the function of the receptor, so we hypothesized that targeting TREM2 to increase its function might be a valid treatment for Alzheimer’s,” explained Dr. Donna Wilcock, associate director of the University of Kentucky’s Sanders-Brown Center on Aging (SBCoA).
Researchers found that the therapeutic targeting of TREM2 using a TREM2-activating antibody leads to the activation of microglia, recruitment of microglia to amyloid plaques, reduced amyloid deposition, and ultimately improved cognition.
“The big takeaway is that this is the first approach that targets TREM2 to promote microglia to clear the amyloid deposits in the brain that are thought to be the cause of Alzheimer’s,” said Wilcock.
The biopharmaceutical company Alector developed the antibody for this study which was conducted on mice. Due to the study’s success, SBCoA is set to be a site for an upcoming clinical trial using this new approach.