In the March 22 edition of Neuron, researchers at the San Francisco VA Medical Center and the University of California, San Francisco, reveal that a new magnetic resonance imaging (MRI) technique based on whole-brain tractography that maps the “communication wires” (neural pathways) that connect different regions of the brain, may predict the rate of progression and physical path of many degenerative brain diseases.

The technique was developed by SFVAMC researchers together with a team led by Bruce Miller, M.D., clinical director of the UCSF Memory and Aging Center. According to the researchers, the new technique supports growing evidence that dementias spread through the brain along specific neuronal pathways in the same way as prion diseases do.

Using images of 14 healthy brains, the researchers used the technique to realistically predict the physical progression of Alzheimer’s disease and frontotemporal dementia (FTD). They found that the disease progress closely matched actual MRI imagines of brain degeneration in 18 patients with FTD and 18 patients with Alzheimer’s disease.

Senior author Michael Weiner, M.D., director of the SFVAMC Center for Imaging of Neurodegenerative Diseases, and UCSF professor of radiology, medicine, psychiatry and neurology, explained:

“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.

This would be extremely useful in planning treatment, and in helping patients with families know what to expect as dementia progresses.”

According to Weiner, 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 agent composed of protein in a misfolded form. These proteins leave harmful amyloid deposits in the brains, which cause degeneration and ultimately death. The prion was discovered and characterized by neurologist Stanley B. Prusiner of UCSF. In 1997, Prusiner was awarded the Nobel Prize in Medicine for his finding.

Prions are responsible for BSE (mad cow) disease in cattle and for Creutzfeldt-Jakob disease in humans. Prusiner’s discovery demonstrated that a protein could cause infection, rather than just the molecules DNA and RNA. Weiner, said:

“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 flow along certain networks in the brain.

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 highlights that FTD and Alzheimer’s “are not infectious diseases” like Creutzfeldt-Jakob. However, Weiner explains: “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.”

Ashish Raj, Ph.D., of SFVAMC and UCSF at the time of the study and at present, at Weill Medical College, Cornell University, NY, is lead author of the report; the co-author is Amy Kuceyeski of Weill Cornell.

The study received funding from the National Institutes of Health, some of which were administered by the Northern California Institute for Research and Education, as well as from the UCSF California Alzheimer’s Disease Research Center.

Written By Grace Rattue