Computer Modeling Supports Theory That Many Dementias Spread Like Prion Diseases
A new technique for analyzing brain images offers the possibility of using magnetic resonance imaging (MRI) to predict the rate of progression and physical path of many degenerative brain diseases, report scientists at Weill Medical College, Cornell University, NY, the San Francisco VA Medical Center and the University of California, San Francisco.
The scientists say the study supports mounting evidence that dementias spread through the brain along specific neuronal pathways in the same manner as prion diseases (see related UCSF story).
Led by Ashish Raj, PhD, of Weill Cornell, the scientists employed new computer modeling techniques developed by Raj in collaboration with a team led by Bruce Miller, MD, clinical director of the UCSF Memory and Aging Center. Using data supplied by SFVAMC researchers, the team applied the new methods to successfully predict the physical progression of Alzheimer’s disease and frontotemporal dementia (FTD) based on images of 14 healthy brains.
The models were based on whole-brain tractography, an MRI technique that maps the neural pathways, or “communication wires,” that connect different areas of the brain. The spread of disease along those pathways, as predicted by the models, closely matched actual MRI images of brain degeneration in 18 Alzheimer’s patients and 18 FTD patients.
The study was published in the March 22 edition of Neuron.
“The results need to be replicated, but they suggest that, by using this approach, we can predict the location and course of future brain atrophy in Alzheimer’s, FTD and other degenerative brain diseases, based on just one MRI taken at the outset of the disease,” said senior author Michael Weiner, MD, director of the SFVAMC Center for Imaging of Neurodegenerative Diseases. “This would be extremely useful in planning treatment, and in helping patients and families know what to expect as dementia progresses.”
Weiner, who is also a UCSF professor of radiology, medicine, psychiatry and neurology, said that the results were “consistent with an emerging concept that brain damage occurs in these neurodegenerative diseases in a diffusive, prion-like propagation.”
A prion is an infectious, misfolded form of a normal protein. These proteins leave destructive amyloid deposits in the brains in which they develop, causing degeneration and eventual death. They are responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, or “mad cow” disease, in cattle. In 1997, neurologist Stanley B. Prusiner of UCSF was awarded the Nobel Prize in Medicine for discovering and characterizing the prion. His finding overturned a tenet of modern biology, showing that a protein, rather than just the molecules DNA and RNA, could cause infection.
“The idea of a prion-like mode of progression in dementias, which many scientists are beginning to support, is that the misfolded protein in one neuron will infect a neighboring brain cell, causing proteins in that cell to misfold in turn, and that the spread of these misfolded proteins flows along certain networks in the brain,” explained Weiner. “For instance, in Alzheimer’s, there is a spread of amyloid protein along the memory network. This paper reinforces the idea that the damage occurs progressively along that network and others.”
Weiner emphasized that Alzheimer’s and frontotemporal dementia “are not infectious diseases” like Creutzfeldt-Jakob. But he said “it may be that a little seed of the disease begins in one neuron in the brain and spreads in a similar way – so it’s infectious within the brain, from one neuron to the next.”
The co-author of the paper is Amy Kuceyeski of Weill Cornell.
The study was supported in part by funds from the National Institutes of Health, some of which were administered by the Northern California Institute for Research and Education. The UCSF California Alzheimer’s Disease Research Center also supported and contributed to the study.
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