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

TLDR

Neuroinflammatory processes are common in neurodegenerative diseases, but it is unclear whether cerebrospinal fluid (CSF) levels of neuroinflammatory proteins differ in Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The study aimed to identify and characterize neuroinflammatory signatures in CSF from patients with AD, mild cognitive impairment (MCI), and FTD. Researchers measured 92 inflammatory proteins in CSF from 42 AD, 29 MCI/AD, 22 stable MCI, 42 FTD, and 49 control subjects using proximity extension assay and ANOVA, adjusting for age, gender, collection unit, and multiple testing. MMP‑10 was elevated in AD, MCI/AD, and FTD versus controls; additional proteins rose in MCI/AD versus MCI, while FTD exhibited 36 proteins decreased, indicating distinct CSF inflammatory profiles between FTD and AD that suggest divergent neuroinflammatory mechanisms.

Abstract

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.