Why Does White Matter... Matter?
The aging brain's loss of white matter and impact on brain function
As Andreas Vesalius peeled the skull off a human cadaver, he would discover the oddly whitish hue of parts of the brain. Known as the founder of modern human anatomy, Vesalius was the first to properly categorize the human brain, as dissection was previously highly restricted to apes. In his 1543 work “De Humani Corporis Fabrica,” which translates to “On The Fabric Of The Human Body,” Vesalius noted the difference in coloration while doing transverse cuts of the brain.
Imagine a wire without insulation, current would leak out of the wire, and the proper signal wouldn’t reach its final destination. This is similar to white matter in the brain, an insulating fatty substance that maintains signal strength and facilitates communication between areas of the brain.
The brain communicates through neurons, the main cells of the brain, which utilize electrochemical signals. Dendrites, which lie on the cell body, receive the signals. Once a signal is received, the cell body processes and integrates the information. Gray matter primarily consists of dendrites and cell bodies.
Axons transmit signals to neighboring cells’ dendrites. White matter is composed of axons surrounded by a fatty substance called myelin. Myelin has several important functions, including speeding up the transmission of signals, physically protecting nerves, and preventing signals from leaking out and losing their strength. White matter is crucial for communication between different brain regions and processing multisensory stimuli, like connecting a scene in a movie to the audio playing along with it.
Myelin is a structure formed by specific types of glial cells, supporting cells in the brain that are not neurons. Without myelin surrounding the axons of neurons, the brain would not be able to communicate as quickly or effectively. This is the case in demyelinating diseases like multiple sclerosis (MS), which leads to several cognitive issues, muscle fatigue, weakness, and more.
As the brain ages, the volume of white matter decreases, and with it, the amount of myelin. This volume rapidly increases until age 30, where it remains constant, and then begins a sudden decline after age 50. Decreases in white matter tend to be associated with increased ventricular volume. In healthy functioning, the ventricles are hollow chambers in the brain that transport cerebrospinal fluid (CSF). CSF provides cushioning, transports waste, immune protection, and supplies nutrients like oxygen. However, unhealthy increases in ventricular volume are commonly associated with dementia.
Changes to neurons and glial cells lead to a variety of anatomical changes, commonly resulting in loss of white matter and an increase in ventricular volume. Examples include less creation of myelin, degeneration of the axon, and inflammation. These changes in function result from several different cellular processes, which I will dive further into in the coming posts.
These issues are at the core of research for studying neurodegenerative diseases like AD and Parkinson’s. Researchers are carefully studying the aging brain and seeking to understand changes to cell functioning. Through these methods, better treatment options can be made available for those living with these conditions.
Vesalius would be pleased to know how far his discovery of white matter has come. As neuroscientists deepen their understanding of white matter loss, they can develop treatment options to mitigate the cognitive impact of aging and reduce the likelihood of dementia.
Stay tuned for next week to learn about some of the groundbreaking diagnostic measures clinicians are beginning to use to diagnose Alzheimer’s even before symptoms start.
Sources:
Grey Matter In The Brain. (2023, September 18). https://www.simplypsychology.org/what-is-grey-matter-in-the-brain.html
Groh, J., & Simons, M. (2025). White matter aging and its impact on brain function. Neuron, 113(1), 127–139. https://doi.org/10.1016/j.neuron.2024.10.019
Neuron. (2024). In Simple English Wikipedia, the free encyclopedia. https://simple.wikipedia.org/w/index.php?title=Neuron&oldid=9939708