Could These Proteins Be behind Dementia in Your 40s or 50s?

A new UCSF-led study funded by the NIH has uncovered changes in spinal fluid proteins that could signal the disease’s onset early. The study was published in the journal Nature Aging.

Dementia is typically seen in older adults, but when it appears in middle age, it’s often missed or misdiagnosed. The most common form in these younger cases is frontotemporal dementia (FTD), which can look like depression, schizophrenia, or even Parkinson’s disease before the correct diagnosis is made.

Now, thanks to an NIH-funded study, researchers at UC San Francisco have uncovered promising new clues about how FTD begins. Their discovery could lead to better tools for diagnosis and help more patients join clinical trials earlier.

To understand how FTD develops, the team analyzed spinal fluid from 116 people with inherited FTD and compared it to samples from 39 of their healthy relatives. Since these cases were inherited, the diagnosis was genetically confirmed. This gave scientists a rare opportunity to study the disease in living patients, something that isn’t possible with non-inherited forms of FTD, which can only be confirmed after death.

The analysis revealed changes in over 4,000 proteins. Many of the altered proteins were linked to problems with RNA regulation, which controls how genes are expressed in the brain. Others pointed to disruptions in how brain cells connect and communicate. These changes could serve as the earliest biological signs of FTD, emerging long before symptoms are clearly visible in middle age.

“FTD affects people in the prime of their lives, stripping them of their independence,” said Rowan Saloner, PhD, professor in the UCSF Memory and Aging Center and corresponding author of the paper. “But there’s no definitive way to diagnose it in living patients, unlike other dementias like Alzheimer’s disease.”

“If we’re able to identify FTD early on, perhaps using some of the proteins we’ve identified, we can direct patients to the right resources, get them into the right therapeutic trials, and, ultimately, we hope, provide them with precision treatments.”

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