Abstract
Introduction: Plasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non-dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (Aβ) burden on plasma NfL are lacking. Methods: Associations were tested between plasma NfL and brain Aβ, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. Results: We found that participants with either MTA (defined as MTA score ≥2; neurodegeneration [N]+WMH−) or WMH (cut-off for log-transformed WMH volume at 50th percentile; N−WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH−, N−WMH+, and N−WMH− individuals. Discussion: Plasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment.
| Original language | English |
|---|---|
| Article number | e12396 |
| Journal | Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2023 |
Bibliographical note
Funding Information:We acknowledge the following teams or individuals for their contributions to study: the patients and their families for their participation in this study; the NUS CIRC radiochemistry and QA team for the production and supply of radioligands, and specifically Dr. Akbar Kulasi (quality assurance), David James Green (radioisotope production/cyclotron), Elaine Jia Hui Tan (quality control), and Mohd Fadli Bin Mohammad Noh (manufacturing) for contributing to the different aspects of the synthesis of [F]flutafuranol; and the coordinators and raters teams from Memory, Ageing and Cognition Centre for participant recruitment and assessment. This study was supported by the National Medical Research Council (MOH‐000500‐001, MOH‐000707‐01, and NMRC/CSA‐SI/007/2016 to Drs Chen and Lai; and NMRC/CG/M006/2017, NMRC/CG/013/2013, and NMRC/CG/NUHS/2010 to Dr. Chen). Dr. Ashton is supported by the Swedish Alzheimer Foundation (Alzheimerfonden), the Swedish Brain Foundation (Hjärnfonden), the Swedish Dementia Foundation (Demensförbundet), and Gamla Tjänarinnor Foundation. Dr. Karikari holds a research fellowship from the BrightFocus Foundation (#A2020812F) and is further supported by the Swedish Research Council (Vetenskapsrådet #2021‐03244), the Alzheimer's Association Research Fellowship (#AARF‐21‐850325), Swedish Alzheimer Foundation (Alzheimerfonden; #AF‐930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020‐0240), the Swedish Dementia Foundation (Demensförbundet), the Swedish Parkinson Foundation (Parkinsonfonden; #1252/20), Gamla Tjänarinnor Foundation, the Aina (Ann) Wallströms and Mary‐Ann Sjöbloms Foundation, the Agneta Prytz‐Folkes & Gösta Folkes Foundation (#2020‐00124), the Gun and Bertil Stohnes Foundation, and the Anna Lisa and Brother Björnsson's Foundation. Prof Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018‐02532), the European Research Council (#681712 and #101053962), Swedish State Support for Clinical Research (#ALFGBG‐71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809‐2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF‐21‐831376‐C, #ADSF‐21‐831381‐C and #ADSF‐21‐831377‐C), the Olav Thon Foundation, the Erling‐Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019‐0228), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021‐00694), and the UK Dementia Research Institute at UCL (UKDRI‐1003). Prof Blennow is supported by the Swedish Research Council (#2017‐00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB‐201809‐2016615), the Swedish Alzheimer Foundation (#AF‐742881), Hjärnfonden, Sweden (#FO2017‐0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF‐agreement (#ALFGBG‐715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019‐466‐236), and the Alzheimer's Association 2021 Zenith Award (ZEN‐21‐848495). The work is supported by National University Health System Center grant SEED funding (A‐0006090‐00‐00), NUS start‐up grant (R‐608‐000‐257‐133), National Medical Research Council Singapore, Transition Award (A‐0006310‐00‐00) and Ministry of Education, Academic Research Fund Tier 1 (A‐0006106‐00‐00) awarded to Dr. Hilal. Role of the funder/sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.
