How do middle-aged folks get dementia? It could be these proteins
- Date:
- May 16, 2025
- Source:
- University of California - San Francisco
- Summary:
- Dementia usually affects older people, so when it occurs in middle age, it can be hard to recognize. 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.
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Dementia usually affects older people, so when it occurs in middle age, it can be hard to recognize. 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 4,000 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 -- required for the proper expression of genes in the brain -- 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 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."
The patients came from the ALLFTD Consortium, which is helmed by study co-authors Adam Boxer, MD, PhD, and Howie Rosen, MD, of UCSF, and Brad Boeve, MD, of the Mayo Clinic. Kaitlin Casaletto, PhD, professor in the UCSF Memory and Aging Center, is the senior author of the study.
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Materials provided by University of California - San Francisco. Original written by Levi Gadye. Note: Content may be edited for style and length.
Journal Reference:
- Rowan Saloner, Adam M. Staffaroni, Eric B. Dammer, Erik C. B. Johnson, Emily W. Paolillo, Amy Wise, Hilary W. Heuer, Leah K. Forsberg, Argentina Lario-Lago, Julia D. Webb, Jacob W. Vogel, Alexander F. Santillo, Oskar Hansson, Joel H. Kramer, Bruce L. Miller, Jingyao Li, Joseph Loureiro, Rajeev Sivasankaran, Kathleen A. Worringer, Nicholas T. Seyfried, Jennifer S. Yokoyama, Salvatore Spina, Lea T. Grinberg, William W. Seeley, Lawren VandeVrede, Peter A. Ljubenkov, Ece Bayram, Andrea Bozoki, Danielle Brushaber, Ciaran M. Considine, Gregory S. Day, Bradford C. Dickerson, Kimiko Domoto-Reilly, Kelley Faber, Douglas R. Galasko, Tania Gendron, Daniel H. Geschwind, Nupur Ghoshal, Neill Graff-Radford, Chadwick M. Hales, Lawrence S. Honig, Ging-Yuek R. Hsiung, Edward D. Huey, John Kornak, Walter Kremers, Maria I. Lapid, Suzee E. Lee, Irene Litvan, Corey T. McMillan, Mario F. Mendez, Toji Miyagawa, Alexander Pantelyat, Belen Pascual, Joseph Masdeu, Henry L. Paulson, Leonard Petrucelli, Peter Pressman, Rosa Rademakers, Eliana Marisa Ramos, Katya Rascovsky, Erik D. Roberson, Rodolfo Savica, Allison Snyder, Anna Campbell Sullivan, M. Carmela Tartaglia, Marijne Vandebergh, Brad F. Boeve, Howie J. Rosen, Julio C. Rojas, Adam L. Boxer, Kaitlin B. Casaletto. Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration. Nature Aging, 2025; DOI: 10.1038/s43587-025-00878-2
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