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- W2536210522 abstract "Most patients with frontotemporal lobar degeneration (FTLD) have pathology of TDP-43 or tau aggregation. While each molecular pathology is associated with mutations in specific genes (e.g. GRN and C9orf72 or MAPT) there is clinical overlap between both pathologies, and with Alzheimer’s disease (AD). The only validated biomarker for FTLD is progranulin in blood or cerebrospinal fluid (CSF), which is decreased in patients with a GRN mutation. This study aimed to determine if CSF progranulin levels and other biomarkers are dependent on mutation status only or are related to pathology as well. Definite FTLD patients (n=45), clinically diagnosed AD patients (n=45) and cognitively healthy controls (n=20) were included in this study. FTLD-TDP (n=28, including 10 GRN and 17 C9orf72 mutation carriers), FTLD-tau (n=10) and FTLD-other (n=7) subgroups were defined by genetic carrier status and/or postmortem neuropathological confirmation. CSF and serum levels of progranulin were quantified using Human Progranulin ELISA Kits (Adipogen Inc., Korea). Other biomarkers included routine AD markers (Aβ1-42, hTau and pTau181P, INNOTEST, Fujirebio Europe, Belgium) and NF-light (UmanDiagnostics, IBL International GmbH, Germany). FTLD-GRN patients had the lowest serum and CSF progranulin levels of all groups, which determined the significances when comparing FTLD-TDP and FTLD-tau groups (p<0.05) and when comparing FTLD, AD and controls (p<0.02). Progranulin levels in CSF and serum were significantly correlated in all FTLD subgroups except C9orf72 repeat expansions carriers. CSF levels of markers for neurodegeneration (hTau and NF-light) were highest in FTLD-GRN patients as compared to other FTLD-subgroups (Table 1). A cox hazard regression analysis (corrected for age at onset) in another cohort of dementia patients without motor neuron disease, showed a mean disease duration of 5.6y±2.6y in GRN carriers (n=40) and 8.2y±5.0y in C9orf72 carriers (n=30) (p=0.051) (Figure 1). Our results confirm that CSF and serum progranulin levels can reliably identify GRN mutation carriers in a dementia cohort. The increased CSF levels of tau and NF-light chain in GRN mutation carrying FTLD patients suggest more neurodegeneration in this subgroup. GRN carriers indeed have a shorter disease duration than C9orf72 carriers. Cox hazard regression analysis of disease duration in GRN carriers (n=59) versus C9orf72 carriers (n=53) with pure dementia (p=0.051), corrected for age at onset. Numbers include deceased patients (GRN: n=40; C9orf72: n=30) and living patients censored at time of last evaluation (GRN: n=19; C9orf72: n=23)." @default.
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- W2536210522 date "2016-07-01" @default.
- W2536210522 modified "2023-10-18" @default.
- W2536210522 title "P4-120: Increased CSF Levels of Biomarkers for Neurodegeneration in FTLD-GRN Mutation Carriers" @default.
- W2536210522 doi "https://doi.org/10.1016/j.jalz.2016.06.2211" @default.
- W2536210522 hasPublicationYear "2016" @default.
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