Protein Clues in the Hunt for the Cause of Frontotemporal Dementia
Dementia usually affects older people, so when it occurs in middle age, it can be hard to recognise. The most common form is frontotemporal dementia (FTD), which is often mistaken for depression, schizophrenia, or Parkinson’s disease before the correct diagnosis is reached.
Now, as part of an NIH-funded study, researchers at UC San Francisco have found some clues about how FTD develops that could lead to new diagnostics and get more patients into clinical trials. The findings appear in Nature Aging on May 16.
The team measured more than 4000 proteins found in spinal tap fluid from 116 FTD patients and compared them to those from 39 of their healthy relatives. All 116 patients had inherited forms of FTD, enabling researchers to study the disease in living people with confirmed diagnosis, something that isn’t possible in non-inherited FTD cases, which can only be confirmed after death.
The composition of the proteins that changed in FTD suggest that these patients have problems with RNA regulation along with defects that affect connections in their brains. These proteins, researchers think, could be the first specific markers for FTD that emerge as the disease develops in middle age.
FTD is the most common form of dementia for people under 60. Because it occurs in younger people, it is often misdiagnosed as depression, early-onset Alzheimer’s, Parkinson’s, or a psychiatric condition. It takes an average of 3.6 years for patients to get an accurate diagnosis. There is no cure, and there are no treatments to slow or stop disease progression. It is distinct from Alzheimer’s in 3 major ways:
- FTD features a gradual decline in behavior, language, or movement, but memory is intact.
- It usually strikes younger people, between 45 and 65 years of age, and is less likely to strike after 65.
- It’s less common, affecting 60 000 people in the U.S. (Alzheimer’s affects 6.7 million Americans).
“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.”
