PMID- 37897306 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240406 IS - 1531-8249 (Electronic) IS - 0364-5134 (Print) IS - 0364-5134 (Linking) VI - 95 IP - 2 DP - 2024 Feb TI - Diagnostic Utility of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia. PG - 299-313 LID - 10.1002/ana.26822 [doi] AB - OBJECTIVE: This study was undertaken to apply established and emerging cerebrospinal fluid (CSF) biomarkers to improve diagnostic accuracy in patients with rapidly progressive dementia (RPD). Overlap in clinical presentation and results of diagnostic tests confounds etiologic diagnosis in patients with RPD. Objective measures are needed to improve diagnostic accuracy and to recognize patients with potentially treatment-responsive causes of RPD. METHODS: Biomarkers of Alzheimer disease neuropathology (amyloid-beta 42/40 ratio, phosphorylated tau [p-tau181, p-tau231]), neuroaxonal/neuronal injury (neurofilament light chain [NfL], visinin-like protein-1 [VILIP-1], total tau), neuroinflammation (chitinase-3-like protein [YKL-40], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], glial fibrillary acidic protein [GFAP], monocyte chemoattractant protein-1 [MCP-1]), and synaptic dysfunction (synaptosomal-associated protein 25kDa, neurogranin) were measured in CSF obtained at presentation from 78 prospectively accrued patients with RPD due to neurodegenerative, vascular, and autoimmune/inflammatory diseases; 35 age- and sex-matched patients with typically progressive neurodegenerative disease; and 72 cognitively normal controls. Biomarker levels were compared across etiologic diagnoses, by potential treatment responsiveness, and between patients with typical and rapidly progressive presentations of neurodegenerative disease. RESULTS: Alzheimer disease biomarkers were associated with neurodegenerative causes of RPD. High NfL, sTREM2, and YKL-40 and low VILIP-1 identified patients with autoimmune/inflammatory diseases. MCP-1 levels were highest in patients with vascular causes of RPD. A multivariate model including GFAP, MCP-1, p-tau181, and sTREM2 identified the 44 patients with treatment-responsive causes of RPD with 89% accuracy. Minimal differences were observed between typical and rapidly progressive presentations of neurodegenerative disease. INTERPRETATION: Selected CSF biomarkers at presentation were associated with etiologic diagnoses and treatment responsiveness in patients with heterogeneous causes of RPD. The ability of cross-sectional biomarkers to inform upon mechanisms that drive rapidly progressive neurodegenerative disease is less clear. ANN NEUROL 2024;95:299-313. CI - (c) 2023 American Neurological Association. FAU - Kuchenbecker, Lindsey A AU - Kuchenbecker LA AUID- ORCID: 0000-0002-2987-1040 AD - Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Tipton, Philip W AU - Tipton PW AUID- ORCID: 0000-0003-4084-2248 AD - Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Martens, Yuka AU - Martens Y AD - Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Brier, Matthew R AU - Brier MR AUID- ORCID: 0000-0001-5987-8705 AD - Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Satyadev, Nihal AU - Satyadev N AUID- ORCID: 0000-0001-7302-2348 AD - Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Dunham, S Richard AU - Dunham SR AUID- ORCID: 0000-0003-2840-3955 AD - Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Lazar, Evelyn B AU - Lazar EB AD - Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA. AD - Hackensack Meridian JFK University Medical Center, Edison, NJ, USA. FAU - Dacquel, Maxwell V AU - Dacquel MV AD - Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Henson, Rachel L AU - Henson RL AD - Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Bu, Guojun AU - Bu G AD - Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Geschwind, Michael D AU - Geschwind MD AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. FAU - Morris, John C AU - Morris JC AD - Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Schindler, Suzanne E AU - Schindler SE AD - Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Herries, Elizabeth AU - Herries E AD - Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. FAU - Graff-Radford, Neill R AU - Graff-Radford NR AD - Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA. FAU - Day, Gregory S AU - Day GS AUID- ORCID: 0000-0001-5133-5538 AD - Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA. LA - eng GR - P30 AG066444/AG/NIA NIH HHS/United States GR - K23 NS128325/NS/NINDS NIH HHS/United States GR - P30AG062677/AG/NIA NIH HHS/United States GR - P30AG066444/AG/NIA NIH HHS/United States GR - K23 AG064029/AG/NIA NIH HHS/United States GR - P30 AG062677/AG/NIA NIH HHS/United States GR - K23AG064029/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20231110 PL - United States TA - Ann Neurol JT - Annals of neurology JID - 7707449 RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (tau Proteins) RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Alzheimer Disease/diagnosis/cerebrospinal fluid MH - Chitinase-3-Like Protein 1 MH - *Neurodegenerative Diseases MH - tau Proteins/cerebrospinal fluid MH - Cross-Sectional Studies MH - *Dementia MH - Amyloid beta-Peptides/cerebrospinal fluid MH - Biomarkers/cerebrospinal fluid PMC - PMC10842089 MID - NIHMS1941021 COIS- Potential Conflicts of Interest The Authors report no competing interests that are directly relevant to this work. EDAT- 2023/10/29 06:43 MHDA- 2024/01/29 06:43 PMCR- 2025/02/01 CRDT- 2023/10/28 07:42 PHST- 2023/10/13 00:00 [revised] PHST- 2023/08/08 00:00 [received] PHST- 2023/10/22 00:00 [accepted] PHST- 2025/02/01 00:00 [pmc-release] PHST- 2024/01/29 06:43 [medline] PHST- 2023/10/29 06:43 [pubmed] PHST- 2023/10/28 07:42 [entrez] AID - 10.1002/ana.26822 [doi] PST - ppublish SO - Ann Neurol. 2024 Feb;95(2):299-313. doi: 10.1002/ana.26822. Epub 2023 Nov 10.