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.
Highlights
Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are two of our most common neurodegenerative disorders
Women were slightly overrepresented in the AD and mild cognitive impairment (MCI)/AD group (59.5% and 58.6%, respectively), while the FTD group consisted of more men (69.0%) with a slightly lower mean ± standard deviation (SD) age of 64.6 ± 9.0 years (Table 1)
Amyloid-42 (A42) cerebrospinal fluid (CSF) levels were roughly 50% lower in the AD and MCI due to AD (MCI/AD) group compared with the controls (AD: 415 ± 82, MCI/AD: 439 ± 108, Controls: 899 ± 289), while the total-tau (t-tau) levels were approximately 55–85% higher (AD: 725 ± 296, MCI/AD: 608 ± 235, Controls: 392 ± 233, Table 1)
Summary
Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are two of our most common neurodegenerative disorders Whereas both diseases are characterized by neuroinflammatory processes, we have limited knowledge of how these are mirrored in the cerebrospinal fluid (CSF). Only about 50% of all MCI cases progress to AD dementia, whereas the other half remains cognitively stable even after several years of follow-up [3] It is today largely unknown what molecular features, other than A and tau mismetabolism, that distinguish MCI patients with incipient AD from non-progressors. 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. 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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