These Brain Cells May Be Key To Understanding Alzheimer's Progression

Most people have never heard of tanycytes. But these brain cells may hold the key to understanding the progression of Alzheimer's disease.

For decades, scientists have known that the accumulation of the protein tau is a hallmark of Alzheimer's. What they didn't know was how the brain clears tau under normal conditions, and what goes wrong when it doesn't.

Tanycytes are specialized cells located in the hypothalamus, the brain region that regulates everything from hunger to hormone release. Unlike most brain cells, tanycytes bridge two critical compartments: the cerebrospinal fluid (CSF) that bathes your brain and the blood vessels that connect to the rest of your body.

You can think of tanycytes as gatekeepers with very long arms. Their cell bodies line the walls of the brain, while their arms extend outward until they make direct contact with blood vessels.

Tau is a protein that normally helps stabilize the internal scaffolding of neurons. But in Alzheimer's disease, tau becomes abnormally modified and clumps together into a tangle. Under healthy conditions, tau is cleared from the brain. But in Alzheimer's, this clearance fails, and tau accumulates in the CSF and brain tissue.

According to the research, tanycytes collect tau from the cerebrospinal fluid and release it into blood vessels that eventually drain into the body's main circulation system.

The study demonstrated this using fluorescently labeled tau injected into the brains of mice. Within minutes, the tau appeared inside tanycytes, traveled through their long arms, and was released into the bloodstream.

When the team blocked tanycytic transport in mice, tau levels dropped significantly, showing that the tau wasn't able to get out of the brain efficiently with this passageway blocked. Hindering this transport also negatively effected tau in the hippocampus, the brain region essential for memory.

The researchers took this information and applied to it to humans by examining brain tissue from Alzheimer's patients. They found that tanycytes in Alzheimer's patients' brains were fragmented and disorganized, suggesting their internal structure had broken down. The genes involved in the transport of tau were significantly disrupted in these patients' tanycytes.

To confirm that tau clearance was actually impaired in living patients, the team analyzed data from two cohorts of participants. They found that ratios of tau in the blood and CSF were lower in Alzheimer's patients compared to controls, suggesting that tau wasn't being transported efficiently.

This study represents the first time scientists are identifying tanycytes as major players in clearing tau from the brain, which represents a significant shift in how scientists understand Alzheimer's disease.

It's important to note that tanycytes have a job beyond clearing tau. They also transport metabolic hormones from the blood into the brain. These hormones have been proposed to play neuroprotective roles in Alzheimer's. If tanycytes are damaged, it could create a double problem: toxic tau can't get out, and protective signals can't get in.

This discovery won't change your morning routine tomorrow. There's no supplement to boost your tanycytes (yet), and no lifestyle intervention that has been shown to directly protect these cells. But this research is a first step toward future interventions.

This research represents a significant shift in understanding Alzheimer's pathology. It doesn't offer a cure, but it does offer a new target for future therapies and a clearer picture of what goes wrong in the Alzheimer's brain.