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Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia.

Artikel i vetenskaplig tidskrift
Författare Carolin Heller
Martha S Foiani
Katrina Moore
Rhian Convery
Martina Bocchetta
Mollie Neason
David M Cash
David Thomas
Caroline V Greaves
Ione Oc Woollacott
Rachelle Shafei
John C Van Swieten
Fermin Moreno
Raquel Sanchez-Valle
Barbara Borroni
Robert Laforce
Mario Masellis
Maria Carmela Tartaglia
Caroline Graff
Daniela Galimberti
James B Rowe
Elizabeth Finger
Matthis Synofzik
Rik Vandenberghe
Alexandre de Mendonca
Fabrizio Tagliavini
Isabel Santana
Simon Ducharme
Christopher R Butler
Alex Gerhard
Johannes Levin
Adrian Danek
Giovanni Frisoni
Sandro Sorbi
Markus Otto
Amanda J Heslegrave
Henrik Zetterberg
Jonathan D Rohrer
Publicerad i Journal of neurology, neurosurgery, and psychiatry
Volym 91
Nummer/häfte 3
Sidor 263-270
ISSN 1468-330X
Publiceringsår 2020
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 263-270
Språk en
Länkar dx.doi.org/10.1136/jnnp-2019-321954
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Neurokemi

Sammanfattning

There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker.Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enrolled in the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation carriers (88 presymptomatic, 31 symptomatic), 53 MAPT mutation carriers (34 presymptomatic, 19 symptomatic) and 183 non-carrier controls. Biomarker measures were compared between groups using linear regression models adjusted for age and sex with family membership included as random effect. Participants underwent standardised clinical assessments including the Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale and MRI. Spearman's correlation coefficient was used to investigate the relationship of plasma GFAP to clinical and imaging measures.Plasma GFAP concentration was significantly increased in symptomatic GRN mutation carriers (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 to 445.6), but not in those with C9orf72 expansions (9.0, -61.3 to 54.6), MAPT mutations (12.7, -33.3 to 90.4) or the presymptomatic groups. GFAP concentration was significantly positively correlated with age in both controls and the majority of the disease groups, as well as with NfL concentration. In the presymptomatic period, higher GFAP concentrations were correlated with a lower cognitive score (MMSE) and lower brain volume, while in the symptomatic period, higher concentrations were associated with faster rates of atrophy in the temporal lobe.Raised GFAP concentrations appear to be unique to GRN-related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials.

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