Newswise — The scene plays out a thousand times each day in physicians’ offices across the country. An anxious spouse or adult child tells a story of memory loss, poor judgment or erratic behavior in an elderly patient. Those in the room may not realize that this moment has been nearly a decade in the making. It follows a desperate battle that the patient’s brain cells have been waging to repair damage caused by the relentless progression of Alzheimer’s disease.

A newly published study by researchers from the UMDNJ-School of Osteopathic Medicine provides evidence of this battle and suggests a promising path for novel therapeutic agents for the disease. Writing in Brain Research, the researchers have identified a protein, vimentin, that normally appears twice in a lifetime – when neurons in the brain are forming during the first years of life and, years later when the brain’s neurons are under siege from Alzheimer’s or other neurodegenerative diseases.

“Vimentin is expressed by neurons in regions of the brain where there is Alzheimer’s damage but not in undamaged areas of the brain,” said Robert Nagele, PhD, a professor at UMDNJ and the study’s corresponding author. “When the patient shows up at the doctor’s office with symptoms of cognitive impairment, the neurons have reached the point where they can no longer keep pace with the ever-increasing damage caused by Alzheimer’s.”

In explaining the findings, Nagele likened neurons to a tree with long strands called dendrites branching off from the main part of the cell. The dendrite branches are covered with 10,000 tiny “leaves” called synapses that allow neurons to communicate with each other. Vimentin is an essential protein for building the dendrite branches that support the synapses.

“A hallmark of Alzheimer’s is the accumulation of amyloid deposits that gradually destroy the synapses and cause the collapse of dendrite branches,” he said. “When the dendrites and synapses degenerate, the neuron releases vimentin in an attempt to re-grow the dendrite tree branches and synapses. It’s a rerun of the embryonic program that allowed the brain to develop in the early years of life.”

The researchers also reported some initial findings that indicated a similar damage response mechanism takes place following traumatic brain injury, suggesting the possibility that similar therapeutic agents could be developed to enhance repair both for sudden brain trauma and for progressive neurodegenerative diseases.

This research was supported by the Alzheimer’s Association, the New Jersey Governor’s Council on Autism, the New Jersey Commission on Science and Technology and the Foundation of UMDNJ. The study’s authors included researchers from UMDNJ, Johnson and Johnson Pharmaceutical Research and Development and the Department of Physiology and Pharmacology at The City University of New York Medical School.

The UMDNJ-School of Osteopathic Medicine is dedicated to providing excellence in medical education, research and health care for New Jersey and the nation. Working in cooperation with Kennedy Memorial Hospitals-University Medical Center, its principal affiliate, the UMDNJ-School of Osteopathic Medicine places an emphasis on primary health care and community health services that reflect its osteopathic philosophy, with centers of excellence that demonstrate its commitment to developing clinically skillful, compassionate and culturally competent physicians from diverse backgrounds, who are prepared to become leaders in their communities.

The University of Medicine and Dentistry of New Jersey (UMDNJ) is the nation's largest free-standing public health sciences university with more than 5,900 students attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and its only school of public health, on five campuses. Last year, there were more than two million patient visits to UMDNJ facilities and faculty at campuses in Newark, New Brunswick/Piscataway, Scotch Plains, Camden and Stratford. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, a mental health and addiction services network.

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Brain Research