학술논문
Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration.
Document Type
article
Author
Asken, Breton; Ljubenkov, Peter; Staffaroni, Adam; Casaletto, Kaitlin; Masdeu, Joseph; Mendez, Mario; Pascual, Belen; Pressman, Peter; Tartaglia, Maria; Kremers, Walter; Forsberg, Leah; Boeve, Brad; Boxer, Adam; Rosen, Howie; Kramer, Joel; Kornak, John; Heuer, Hilary; Shigenaga, Judy; Appleby, Brian; Bozoki, Andrea; Domoto-Reilly, Kimiko; Ghoshal, Nupur; Huey, Edward; Cobigo, Yann; Rojas-Rodriguez, Julio; Rankin, Katherine; Litvan, Irene; Vandevrede, Lawren
Source
Journal of Neurology, Neurosurgery and Psychiatry. 94(7)
Subject
Language
Abstract
BACKGROUND: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). METHODS: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers (MAPT, C9orf72, GRN) and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes). We compared inflammation between asymptomatic carriers who remained clinically normal (asymptomatic non-converters) and those who became symptomatic (asymptomatic converters) using area under the curve analyses. Discrimination accuracy was compared with that of plasma neurofilament light chain (NfL). RESULTS: We studied 394 participants (non-carriers=143, C9orf72=117, GRN=62, MAPT=72). In MAPT, higher TNFα was associated with faster functional decline (B=0.12 (0.02, 0.22), p=0.02) and temporal lobe atrophy. In C9orf72, higher TNFα was associated with faster functional decline (B=0.09 (0.03, 0.16), p=0.006) and cognitive decline (B=-0.16 (-0.22, -0.10), p