Alzheimer’s can develop in a person as early as their 30s and often fully show signs in their mid-60s. Extreme forgetfulness, especially navigating daily life, results from dying neurons and shrinking brain regions. In recent reports, an estimated 65 million Americans have a degenerative neurological disease, and seventy-three percent are 75 years old and above. The data was gathered in 2022 by the Alzheimer’s Association, which provided sufficient information to spread awareness. Due to the increasing number of cases, researchers are more motivated to find answers between a genetic variation and Alzheimer’s disease. The investigation will aid in understanding the root cause of neurodegeneration in early Alzheimer’s.
In a new research project, scientists accumulated information through fruit fly models. Specialists from the Australian National University, the University of Melbourne, and the Walter Eliza Hall Institute of Medical Research led the investigation. The team’s paper was published in Scientific Reports. Figuring out the cause of dying brain cells and quality control pathways can help devise a cure or further treatment for the degenerative disease.
“Currently, we don’t have good treatments for Alzheimer’s, and we urgently need new options,” lead researcher Doctor Agalya Periasamy stated. “Our research offers a possible alternative avenue for development of much-needed therapeutic interventions for this devastating disease.” There is missing information about dying neurons, because the mitochondrial TOMM40 gene is difficult to separate from an Alzheimer’s gene called ApoE. The gene is an indicator of late-onset Alzheimer’s. However, based on their findings, a shrinking brain results from extreme TOMM40 buildup.
To dig deeper, the research team utilized fruit flies to determine the relationship between TOMM40 levels and Alzheimer’s. The model was inspired by how fruit fly eyes consist of photoreceptors which are specially designed neurons. Fruit fly models are assigned to produce Tom40 protein, the substance built by TOMM40. They’ll observe the changes that will occur once there’s too much Tom40 production. One of their findings showed that high protein levels resulted in cell death in the retina. The effect also depends on how much protein the cell was exposed to.
“We looked at the eyes of fly larvae under the microscope and found an increase in a protein that marks the activation of apoptosis, called ‘caspase-3’ in humans. This confirmed to us that apoptosis was the missing link we were looking for,” Dr. Periasamy said. Furthermore, the team witnessed the impact of Tom40, which showed that compound production alters the balance in the mitochondria and later triggers apoptosis. However, according to Dr. Jacqui Gilbis, the study might have discovered the cause of too much Tom40; they still needed to prove how protein contributes to neurodegeneration.
“Our findings identify a new entry point into cell quality control pathways that could be targeted to interrupt TOMM40-induced neurodegeneration,” Dr. Gilbis said. “While this research is still in its early stages, it will be exciting to explore and tap into the relationship between TOMM40-linked apoptosis and Alzheimer’s disease to set the groundwork for the development of new therapies for cognitive conditions,” she added.