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Review
. 2022 Jan;21(1):66-77.
doi: 10.1016/S1474-4422(21)00361-6. Epub 2021 Nov 24.

Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

Charlotte E Teunissen  1 , Inge M W Verberk  2 , Elisabeth H Thijssen  2 , Lisa Vermunt  2 , Oskar Hansson  3 , Henrik Zetterberg  4 , Wiesje M van der Flier  5 , Michelle M Mielke  6 , Marta Del Campo  7
Affiliations
Review

Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

Charlotte E Teunissen et al. Lancet Neurol. 2022 Jan.

Abstract

For many years, blood-based biomarkers for Alzheimer's disease seemed unattainable, but recent results have shown that they could become a reality. Convincing data generated with new high-sensitivity assays have emerged with remarkable consistency across different cohorts, but also independent of the precise analytical method used. Concentrations in blood of amyloid and phosphorylated tau proteins associate with the corresponding concentrations in CSF and with amyloid-PET or tau-PET scans. Moreover, other blood-based biomarkers of neurodegeneration, such as neurofilament light chain and glial fibrillary acidic protein, appear to provide information on disease progression and potential for monitoring treatment effects. Now the question emerges of when and how we can bring these biomarkers to clinical practice. This step would pave the way for blood-based biomarkers to support the diagnosis of, and development of treatments for, Alzheimer's disease and other dementias.

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Conflict of interest statement

Declarations of interests Research of CET is supported by grants from the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), JPND, Health∼Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, and the Alzheimer's Association. CET is associate editor at Alzheimer's Research & Therapy and Neurology: Neuroimmunology & Neuroinflammation and an advisor for Medidact. CET has a collaboration contract with ADx Neurosciences and Quanterix, and performed contract research for AC-Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Roche, Toyama, and Vivoryon. CET and WMvdF are recipients of ABOARD, which is a public–private partnership (PPP) receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. IMWV received a research grant by Alzheimer Nederland (NL-17004). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation, USA (#201809-2016862); the Alzheimer's disease 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); and the UK Dementia Research Institute at UCL. HZ has served at scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. BBS has no business but owns the hybridomas for some antibodies generated in research. However, these clones are not part of any commercial products. Research programmes of WMvdF have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, Stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, and Combinostics. WMvdF holds the Pasman chair. WMvdF has performed contract research for Biogen MA and Boehringer Ingelheim. WMvdF has been an invited speaker at Boehringer Ingelheim, Biogen MA, Eisai, Danone, and WebMD Neurology (Medscape). WMvdF is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA. WMvdF is an associate editor at Brain. All funding is paid to her institution. OH's work at Lund University was supported by the Swedish Research Council (2016-00906), the Knut and Alice Wallenberg foundation (2017-0383), the Marianne and Marcus Wallenberg foundation (2015.0125), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation (AF-939932), the Swedish Brain Foundation (FO2019-0326), the Parkinson foundation of Sweden (1280/20), the Skåne University Hospital Foundation (2020-O000028), Regionalt Forskningsstöd (2020-0314), and the Swedish federal government under the ALF agreement (2018-Projekt0279). OH has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Alzpath, Biogen, Cerveau, and Roche. MMM has served as a consultant for Biogen and the Brain Protection Company and receives research support from the US National Institute on Aging (U01 AG06786, P30 AG62677, U54AG44170). MdC is supported by the attraction talent fellowship of Comunidad de Madrid (2018-T2/BMD-11885) and San Pablo CEU University. The other authors declare no competing interests.

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