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Plasma biomarker profiles in autosomal dominant Alzheimer's disease

Plasma biomarker profiles in autosomal dominant Alzheimer's disease


Title: Plasma biomarker profiles in autosomal dominant Alzheimer's disease
Author: Johansson, Charlotte
Þórðardóttir, Steinunn
Laffita-Mesa, José
Rodriguez-Vieitez, Elena
Zetterberg, Henrik
Blennow, Kaj
Graff, Caroline
Date: 2023-03-01
Language: English
Scope: 9
Department: Geriatric and Rehabilitation Services
Series: Brain; 146(3)
ISSN: 0006-8950
DOI: https://doi.org/10.1093/brain/awac399
Subject: Öldrunarlæknisfræði; Alzheimer Disease/metabolism; Amyloid beta-Peptides; Biomarkers; Genes, Dominant; Humans; tau Proteins; autosomal dominant Alzheimer's disease; neurofilament light chain; tau; plasma biomarker; glial fibrillary acidic protein; Neurology (clinical)
URI: https://hdl.handle.net/20.500.11815/3943

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Citation:

Johansson , C , Þórðardóttir , S , Laffita-Mesa , J , Rodriguez-Vieitez , E , Zetterberg , H , Blennow , K & Graff , C 2023 , ' Plasma biomarker profiles in autosomal dominant Alzheimer's disease ' , Brain , vol. 146 , no. 3 , pp. 1132-1140 . https://doi.org/10.1093/brain/awac399

Abstract:

Emerging plasma biomarkers of Alzheimer's disease might be non-invasive tools to trace early Alzheimer's disease-related abnormalities such as the accumulation of amyloid-beta peptides, neurofibrillary tau tangles, glial activation and neurodegeneration. It is, however, unclear which pathological processes in the CNS can be adequately detected by peripheral measurements and whether plasma biomarkers are equally applicable in both clinical and preclinical phases. Here we aimed to explore the timing and performance of plasma biomarkers in mutation carriers compared to non-carriers in autosomal dominant Alzheimer's disease. Samples (n = 164) from mutation carriers (n = 33) and non-carriers (n = 42) in a Swedish cohort of autosomal dominant Alzheimer's disease (APP p.KM670/671NL, APP p.E693G and PSEN1 p.H163Y) were included in explorative longitudinal analyses. Plasma phosphorylated tau (P-tau181), total tau (T-tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) concentrations were measured with a single-molecule array method as previously described. Plasma biomarkers were additionally correlated to Alzheimer's disease core biomarkers in the CSF. Results from the longitudinal analyses confirmed that plasma P-tau181, NfL and GFAP concentrations were higher in mutation carriers compared to non-carriers. This change was observed in the presymptomatic phase and detectable first as an increase in GFAP approximately 10 years before estimated symptom onset, followed by increased levels of P-tau181 and NfL closer to expected onset. Plasma P-tau181 levels were correlated to levels of P-tau181 and T-tau in the CSF. Altogether, plasma P-tau181, GFAP and NfL seem to be feasible biomarkers to detect different Alzheimer's disease-related pathologies already in presymptomatic individuals. Interestingly, changes in plasma GFAP concentrations were detected prior to P-tau181 and NfL. Our results suggest that plasma GFAP might reflect Alzheimer's disease pathology upstream to accumulation of tangles and neurodegeneration. The implications of these findings need additional validation, in particular because of the limited sample size.

Description:

© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. Funding Information: H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish regional ALF-agreements (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF, USA) (#201809-2016862), the AD Strategic Fund by the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olaf Thon Foundation (Norway), the Erling-Persson Family Foundation (Sweden), Stiftelsen for Gamla Tjanarinnor (Sweden), the Swedish Brain Foundation (#FO2019-0228), the HORIZON EUROPE Marie Sklodowska Curie Actions research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 860197 (MIRIADE) and the UK Dementia Research Institute (United Kingdom). K.B. is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF, USA) (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721 and #AF-968270), the Swedish Brain Foundation (#FO2017-0243 and #ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240), the EU Joint programme — Neurodegenerative Disease Research (Belgium) (JPND2019-466-236), the National Institute of Health (NIH, USA) (grant #1R01AG068398-01) and the Alzheimer's Association Award (USA) (ZEN-21-848495). C.G. and C.J. are supported by grants from the Swedish Research Council (#529-2014-7504, #2015-02926, #2018-02754), the Swedish Brain Foundation, the Swedish Dementia Foundation, the Swedish Alzheimer Foundation, ALF-Project (Region Stockholm, Sweden), the Gun and Bertil Stohne's Foundation (Sweden) and Stiftelsen for Gamla Tjanarinnor (Sweden). E.R.V. is supported by grants from the Swedish Alzheimer Foundation, the Swedish Dementia Foundation and ALF-project (Region Stockholm, Sweden). Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.

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