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- Remnestål, Julia, et al.
(författare)
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Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers
- 2020
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Ingår i: Translational Neurodegeneration. - : Springer Nature. - 2047-9158. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers. Methods: Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD (bvFTD, n = 16) and progressive primary aphasia (PPA, n = 13), as well as presymptomatic mutation carriers (PMC, n = 16) and non-carriers (NC, n = 8). A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples. The findings were further examined in an independent cohort including 13 FTD patients, 79 patients with Alzheimer's disease and 18 healthy controls. Results: We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals (PMC and NC) for 26 proteins. The analysis show patterns of separation between unaffected individuals and FTD patients, especially for those with a clinical diagnosis of bvFTD. The most statistically significant differences in protein levels were found for VGF, TN-R, NPTXR, TMEM132D, PDYN and NF-M. Patients with FTD were found to have higher levels of TN-R and NF-M, and lower levels of VGF, NPTXR, TMEM132D and PDYN, compared to unaffected individuals. The main findings were reproduced in the independent cohort. Conclusion: In this pilot study, we show a separation of FTD patients from unaffected individuals based on protein levels in CSF. Further investigation is required to explore the CSF profiles in larger cohorts, but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.
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| 2. |
- Vilaplana, Eduard, et al.
(författare)
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Cortical microstructural correlates of astrocytosis in autosomal-dominant Alzheimer disease
- 2020
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Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 94:19, s. e2026-E2036
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the macrostructural and microstructural MRI correlates of brain astrocytosis, measured with C-11-deuterium-L-deprenyl (C-11-DED)-PET, in familial autosomal-dominant Alzheimer disease (ADAD).Methods: The total sample (n = 31) comprised ADAD mutation carriers (n = 10 presymptomatic, 39.2 10.6 years old; n = 3 symptomatic, 55.5 2.0 years old) and noncarriers (n = 18, 44.0 +/- 13.7 years old) belonging to families with mutations in either the presenilin-1 or amyloid precursor protein genes. All participants underwent structural and diffusion MRI and neuropsychological assessment, and 20 participants (6 presymptomatic and 3 symptomatic mutation carriers and 11 noncarriers) also underwent C-11-DED-PET.Results: Vertex-wise interaction analyses revealed a differential relationship between carriers and noncarriers in the association between C-11-DED binding and estimated years to onset (EYO) and between cortical mean diffusivity (MD) and EYO. These differences were due to higher C-11-DED binding in presymptomatic carriers, with lower binding in symptomatic carriers compared to noncarriers, and to lower cortical MD in presymptomatic carriers, with higher MD in symptomatic carriers compared to noncarriers. Using a vertex-wise local correlation approach, C-11-DED binding was negatively correlated with cortical MD and positively correlated with cortical thickness.Conclusions: Our proof-of-concept study is the first to show that microstructural and macrostructural changes can reflect underlying neuroinflammatory mechanisms in early stages of Alzheimer disease (AD). The findings support a role for neuroinflammation in AD pathogenesis, with potential implications for the correct interpretation of neuroimaging biomarkers as surrogate endpoints in clinical trials.
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