Using an unprecedented set of data, researchers from multiple universities have made important discoveries about how the brain's connectivity is influenced by specific proteins and molecular structures.

Upstate Medical University’s Christopher Gaiteri, PhD, working with researchers from Rush University and the University of Alabama at Birmingham have recently published a study exploring how small-scale molecular and cellular processes in the brain contribute to large-scale communication between different brain regions. This work, featured in the November issue of Nature Neuroscience, could lay the groundwork for major advancements for the treatment and prevention of brain disorders like Alzheimer’s disease, dementia, mood disorders, and more. Gaiteri is an associate professor of psychiatry and behavioral sciences at Upstate and an assistant professor at Rush University in its Alzheimer’s disease center.

For the first time, data from various scales; genetics, proteins, brain imaging, and cellular structures, were combined for the same individuals. This approach offers a detailed map of how molecules and structures in the brain support its larger functions.

“fMRI neuroimaging tracks brain activity of people; they need to be alive for that, but you essentially never get brain biopsies from living people.  That means some of our major approaches to Alzheimer's are disconnected,” explains Gaiteri. “We're missing that middle piece of molecular biology, which explains how genetics exert their influence.  In this study, we have that missing middle piece.”

One key finding is the impact of dendritic spines. Dendritic spines are tiny structures on brain cells that play a central role in communication and plasticity (the brain's ability to adapt). This study showed that the shape and density of these spines influence brain connectivity.

How could this help Alzheimer’s and dementia patients? “[Dendritic spines’] shape and the proteins in them could explain the level of synchrony between two brain regions,” said Gaiteri. In biology, synchrony refers to the coordinated firing of neurons across different brain regions. “That matters because synchrony is one of the closest things we can measure in terms of cognition, and because our study suggests which protein and brain structures you would want to target to control that brain communication.”

These findings are the result of incredible coordination and communication.

“The study's lead author, Bernard Ng [PhD, assistant professor at Rush University], is an expert in neuroimaging and molecular biology, so he was holding two pieces of the puzzle.  Six years ago, Jeremy Herskowitz [PhD, associate professor of neurology, University of Alabama at Birmingham] had planned to measure dendritic spines in the same people for whom we had captured neuroimaging, while they were alive.  Shinya Tasaki [PhD, assistant professor at Rush University, Department of Neurological Sciences] and Nick Seyfried [PhD, professor of biochemistry and neurology, Emory University] generated brain protein data on those same people.  With all this data on the same people, we were able to hammer out how they were related.”

The study’s method of integrating data across multiple biological scales could improve future research and drug development, potentially accelerating treatments for cognitive and mental health disorders.

“I hope other scientists take advantage of this neuroimaging data we’ve put in an organized format anyone can use,” says Chris. “Because we've completed a lot of the grunt work, we hope they can quickly roll out their studies using the same dataset.”

The Nature Neuroscience article is available here.