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

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.