Different Inflammatory Signatures in Alzheimer's Disease and Frontotemporal Dementia Cerebrospinal Fluid


Por: Bostrom, G, Freyhult, E, Virhammar, J, Alcolea, D, Tumani, H, Otto, M, Brundin, RM, Kilander, L, Lowenmark, M, Giedraitis, V, Lleo, A, von Arnim, CAF, Kultima, K, Ingelsson, M

Publicada: 1 ene 2021
Resumen:
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.

Filiaciones:
Bostrom, G:
 Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Box 564, SE-75122 Uppsala, Sweden

Freyhult, E:
 Uppsala Univ, Dept Med Sci, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden

Virhammar, J:
 Uppsala Univ Hosp, Dept Neurosci, Neurol, Uppsala, Sweden

Alcolea, D:
 Hosp Santa Creu & Sant Pau, Neurol Dept, Memory Unit, Barcelona, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Tumani, H:
 Ulm Univ Hosp, Dept Neurol, Ulm, Germany

Otto, M:
 Ulm Univ Hosp, Dept Neurol, Ulm, Germany

Brundin, RM:
 Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Box 564, SE-75122 Uppsala, Sweden

Kilander, L:
 Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Box 564, SE-75122 Uppsala, Sweden

Lowenmark, M:
 Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Box 564, SE-75122 Uppsala, Sweden

Giedraitis, V:
 Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Box 564, SE-75122 Uppsala, Sweden

Lleo, A:
 Hosp Santa Creu & Sant Pau, Neurol Dept, Memory Unit, Barcelona, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

von Arnim, CAF:
 Ulm Univ Hosp, Dept Neurol, Ulm, Germany

 Georg August Univ, Univ Med Ctr Gottingen, Dept Geriatr Med, Gottingen, Germany

Kultima, K:
 Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden

Ingelsson, M:
 Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Box 564, SE-75122 Uppsala, Sweden
ISSN: 13872877
Editorial
IOS PRESS, NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 81 Número: 2
Páginas: 629-640
WOS Id: 000669802700017
ID de PubMed: 33814444
imagen Green Published

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