| 1. |
- Benussi, Alberto, et al.
(författare)
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Diagnostic and prognostic value of serum NfL and p-Tau181 in frontotemporal lobar degeneration.
- 2020
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 91:9, s. 960-967
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Tidskriftsartikel (refereegranskat)abstract
- To assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau181 (p-Tau181) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).In this retrospective study, performed on 417 participants, we analysed serum NfL and p-Tau181 concentrations with an ultrasensitive single molecule array (Simoa) approach. We assessed the diagnostic values of serum biomarkers in the differential diagnosis between FTLD, Alzheimer's disease (AD) and healthy ageing; their role as markers of disease severity assessing the correlation with clinical variables, cross-sectional brain imaging and neurophysiological data; their role as prognostic markers, considering their ability to predict survival probability in FTLD.We observed significantly higher levels of serum NfL in patients with FTLD syndromes, compared with healthy controls, and lower levels of p-Tau181 compared with patients with AD. Serum NfL concentrations showed a high accuracy in discriminating between FTLD and healthy controls (area under the curve (AUC): 0.86, p<0.001), while serum p-Tau181 showed high accuracy in differentiating FTLD from patients with AD (AUC: 0.93, p<0.001). In FTLD, serum NfL levels correlated with measures of cognitive function, disease severity and behavioural disturbances and were associated with frontotemporal atrophy and indirect measures of GABAergic deficit. Moreover, serum NfL concentrations were identified as the best predictors of survival probability.The assessment of serum NfL and p-Tau181 may provide a comprehensive view of FTLD, aiding in the differential diagnosis, in staging disease severity and in defining survival probability.
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| 2. |
- Benussi, Alberto, et al.
(författare)
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Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 77:3, s. 1129-1141
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Tidskriftsartikel (refereegranskat)abstract
- It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD).To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD.In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer's disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival.We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival.Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.
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| 3. |
- Swift, Imogen J, et al.
(författare)
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A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
- 2024
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Ingår i: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
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