4.5 Article

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

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 81, Issue 2, Pages 629-640

Publisher

IOS PRESS
DOI: 10.3233/JAD-201565

Keywords

Alzheimer's disease; frontotemporal dementia; mild cognitive impairment; neuroinflammation; proteomics

Categories

Funding

  1. Swedish Alzheimer Foundation [AF-930343]
  2. Swedish Brain Foundation [FO2018-0118]
  3. Gun and Bertil Stohne's Foundation
  4. Geriatriska Fonden
  5. Stiftelsen for Gamla Tjanarinnor
  6. Fondo de Investigaciones Sanitario (FIS), Instituto de Salud Carlos III [PI18/00435, PI17/01896, AC19/00103]
  7. CIBERNED program - Fondo Europeo de Desarrollo Regional, Union Europea, Una Manera de Hacer Europa
  8. German Federal Ministry of Education and Research [FTLDc 01GI1007A, 01ED2008]

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The study revealed that levels of MMP-10 were elevated in AD, MCI/AD, and FTD patients, with additional proteins increased in MCI/AD. In contrast, FTD patients showed decreased levels of 36 proteins, while AD and MCI/AD patients did not show any decrease in protein levels. This suggests distinct patterns of neuroinflammatory processes in different neurodegenerative disorders.
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.

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