How do middle-aged folks get dementia? It could be these proteins

(Press-News.org) 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.  


Authors: Other UCSF authors are Adam Staffaroni, PhD, Emily Paolillo, PhD, Amy Wise, Hilary Heuer, PhD, Argentina Lario Lago, PhD, Julia Webb, Joel Kramer, PsyD, Bruce Miller, MD, Jennifer Yokoyama, PhD, William Seeley, MD, Salvatore Spina, MD, PhD, Lea Grinberg, MD, PhD, Lawren VandeVrede, MD, PhD, Peter Ljubenkov, MD, Suzan Lee, MD, and Julio Rojas, MD, PhD. For all authors, see the paper. 

Funding:   The work was supported in part by the National Institute on Aging, the National Institute of Neurological Diseases and Stroke, the National Center for Advancing Translational Sciences, and the National Institutes of Health (U19 AG063911, U54 NS092089, U01 AG045390, AG038791, AG032306, AG016976, K23AG059888, K23AG073514, AG019724, AG058233, P30 AG062422, R01AG072475, K23AG061253, R01AG032289, R01AG048234, K24AG045333, U24 AG021886). It was also supported by the Alzheimer’s Association, Association for Frontotemporal Degeneration, the BlueField Project to Cure FTD, CurePSP, Larry L. Hillblom Foundation, the Rainwater Charitable Foundation. For all funding, see the paper. 

 

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