Different Inflammatory Signatures in Alzheimer's Disease and Frontotemporal Dementia Cerebrospinal Fluid
Boström, Gustaf (Department of Public Health and Caring Sciences. Geriatrics. Uppsala University)
Freyhult, Eva (Department of Medical Sciences. Science for Life Laboratory. National Bioinformatics Infrastructure Sweden. Uppsala University)
Virhammar, Johan (Department of Neuroscience. Neurology. Uppsala University Hospital)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Tumani, Hayrettin (Department of Neurology. Ulm University Hospital)
Otto, Markus (Department of Neurology. Ulm University Hospital)
Brundin, Rose-Marie (Department of Public Health and Caring Sciences. Geriatrics. Uppsala University)
Kilander, Lena (Department of Public Health and Caring Sciences. Geriatrics. Uppsala University)
Löwenmark, Malin (Department of Public Health and Caring Sciences. Geriatrics. Uppsala University)
Giedraitis, Vilmantas (Department of Public Health and Caring Sciences. Geriatrics. Uppsala University)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Von Arnim, Christine A.F. (Department of Geriatric Medicine. University Medical Center Göttingen. Georg-August-University)
Kultima, Kim (Department of Medical Sciences. Clinical Chemistry. Uppsala University)
Ingelsson, Martin (Department of Public Health and Caring Sciences. Geriatrics. Uppsala University)

Data:	2021
Resum:	Background: Neuroinflammatory processes are common in neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), but current knowledge is limited as to whether cerebrospinal fluid (CSF) levels of neuroinflammatory proteins are altered in these diseases. Objective: To identify and characterize neuroinflammatory signatures in CSF from patients with AD, mild cognitive impairment (MCI), and FTD. Methods: We used proximity extension assay and ANOVA to measure and compare levels of 92 inflammatory proteins in CSF from 42 patients with AD, 29 with MCI due to AD (MCI/AD), 22 with stable MCI, 42 with FTD, and 49 control subjects, correcting for age, gender, collection unit, and multiple testing. Results: Levels of matrix metalloproteinase-10 (MMP-10) were increased in AD, MCI/AD, and FTD compared with controls (AD: Fold change [FC]=1. 32, 95% confidence interval [CI] 1. 14-1. 53, q=0. 018; MCI/AD: FC=1. 53, 95% CI 1. 20-1. 94, q=0. 045; and FTD: FC=1. 42, 95% CI 1. 10-1. 83, q=0. 020). MMP-10 and eleven additional proteins were increased in MCI/AD, compared with MCI (q<0. 05). In FTD, 36 proteins were decreased, while none was decreased in AD or MCI/AD, compared with controls (q<0. 05). Conclusion: In this cross-sectional multi-center study, we found distinct patterns of CSF inflammatory marker levels in FTD and in both early and established AD, suggesting differing neuroinflammatory processes in the two disorders.
Ajuts:	Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI17/01896 Instituto de Salud Carlos III AC19/00103
Nota:	Altres ajuts: Swedish Alzheimer Foundation (AF-930343); Swedish Brain Foundation (FO2018-0118); Gun and Bertil Stohne's Foundation; Geriatriska Fonden; Stiftelsen för Gamla Tjänarinnor; Fondo de Investigaciones Sanitario (FIS); CIBERNED program (Program 1, Alzheimer Disease); Fondo Europeo de Desarrollo Regional (FEDER); German Federal Ministry of Education and Research (grant # FTLDc01GI1007A, Genfi-Prox 01ED2008).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Frontotemporal dementia ; Mild cognitive impairment ; Neuroinflammation ; Proteomics
Publicat a:	Journal of Alzheimer's disease, Vol. 81 Núm. 2 (2021) , p. 629-640, ISSN 1875-8908

DOI: 10.3233/jad-201565
PMID: 33814444

12 p, 801.4 KB

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