Researchers uncover new information about am

INDIANAPOLIS—Experts from the Indiana University School of Medicine have helped identify that a common protein found in neurodegenerative diseases forms amyloid filaments in an age-dependent manner unrelated to the disease.

Many age-related neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are characterized by an abundance of amyloid, or plaque. In a new article published in Natureresearchers from the Molecular Biology Laboratory of the CRM in Cambridge, England, UK and colleagues around the world, including several experts from the IU School of Medicine, have used structure determination by cryo-electron microscopy to discover that the lysosomal transmembrane protein type II , TMEM106B, also forms amyloid filaments in the human brain, but uniquely forms in an age-dependent manner and may not be linked to any type of disease.

“So far, the presence of abundant intraneuronal amyloid filaments in human tissues has always been associated with disease,” said Bernardino Ghetti, MD, Distinguished Professor and Professor of Pathology and Laboratory Medicine at the IU School of Medicine. “While TMEM106B has been associated with frontotemporal dementias and other diseases, evidence for a causal relationship between TMEM106B aggregation and disease now remains unclear.”

The researchers studied 22 people with abundant amyloid deposits, including sporadic and hereditary Alzheimer’s disease, as well as the frontal cortex of three neurologically normal people. They also studied three TMEM106B folds, with no clear relationship between folds and disease. TMEM106B filaments found in the brains of older, but not younger, neurologically normal individuals suggest that these proteins form in an age-dependent manner and that there was no clear relationship between protein folds and neurodegenerative diseases. Previously, TMEM106B had been identified as a risk factor for frontotemporal lobar degeneration, but this research opens the dialogue as the protein may no longer be associated with the cause of a disease.

“This insight encourages us to further evaluate the role of filament formation, like TMEM106B, in relation to human aging and other pathologies, as well as whether they are outside the nervous system,” Ghetti said.

The study was funded by grants from the National Institutes of Health. Other IU School of Medicine study authors include Holly Garringer, Ph.D., Grace Hallinan, PhD, Kathy Newell, MD and Rubén Vidal, PhD. Previously, this research group also explored the pathological differences between hereditary and sporadic Alzheimer’s disease.

Learn more about Alzheimer’s Disease Research at IU School of Medicine.

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IU School of Medicine is the largest medical school in the United States and is ranked among the top medical schools in the nation annually by US News & World Report. The school provides high-quality medical education, access to cutting-edge medical research, and rich campus life in nine Indiana cities, including rural and urban areas consistently recognized for their quality of life.

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