ALZHEIMER’S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING.

Benedet AL, Ashton NJ, Pascoal TA, Leuzy A, Mathotaarachchi S, Kang MS, Therriault J, Savard M, Chamoun M, Schöll M, Zimmer ER, Gauthier S, Labbe A, Zetterberg H, Blennow K and Neto PR

J Neurol. 2019 Sep 26. 

doi: 10.1007/s00415-019-09552-1.

This study was peformed using a Simoa® Homebrew assay.

Abstract

In this study, our aim was to evaluate potential peripheral inflammatory changes in frontotemporal lobar degeneration (FTLD) patients carrying or not the C9orf72 repeat expansion. To this end, levels of several inflammatory markers (MCP-1, RANTES, IL-10, IL-17A, IL-12p, IFN-γ, IL-1β, IL-8, and hs-CRP) and blood cells counts in plasma and/or serum of FTLD patients (N = 98) with or without the C9orf72 repeat expansion were analyzed. In addition, we evaluated whether the analyzed peripheral inflammatory markers correlated with disease progression or distinct clinical phenotypes under the heterogenous FTLD spectrum. Elevated levels of pro-inflammatory RANTES or MCP-1 and decreased levels of anti-inflammatory IL-10 were found to associate with Parkinsonism and a more rapid disease progression, indicated by longitudinal measurements of either MMSE or ADCS-ADL decline. These findings were observed in the total cohort in general, whereas the C9orf72 repeat expansion carriers showed only slight differences in IL-10 and hemoglobin levels compared to non-carriers. Furthermore, these C9orf72 repeat expansion-associated differences were observed mostly in male subjects. The females in general showed elevated levels of several pro-inflammatory markers compared to males regardless of the C9orf72 genotype. Our study suggests that pro-inflammatory changes observed in the early symptomatic phase of FTLD are associated with distinct clinical profiles and a more rapid disease progression, and that the C9orf72 repeat expansion and gender may also affect the inflammatory profile in FTLD.