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Blood-Based Biomarkers for Early Alzheimer’s Disease Diagnosis in Real-World Settings

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Biomarkers for Alzheimer’s Disease Drug Development

Abstract

As our knowledge about the biology of Alzheimer’s disease (AD) expands and we recognize the significance of early intervention for effective treatment, there is a shift in focus toward detecting the disease at an early stage. AD is characterized by the accumulation of misfolded amyloid-β (Aβ) and phosphorylated tau proteins in the brain, leading to the formation of senile plaques and neurofibrillary tangles. While a definitive diagnosis of AD can only be confirmed through autopsy by examining these pathological features, there are now reliable methods available for diagnosing the disease in living individuals. These methods involve analyzing cerebrospinal fluid and using positron emission tomography to accurately assess the presence of Aβ and tau proteins. While these diagnostic markers have shown high accuracy in memory-clinic populations, they do have limitations such as the requirement for invasive lumbar puncture or exposure to ionizing radiation. Additionally, they are not easily accessible outside of specialized healthcare settings. Blood-based biomarkers of the core pathological features of AD are being developed, showing promise for less invasive, scalable identification of AD cases in the community. The advantages for the healthcare systems of this development are obvious, but the diagnostic performance of blood-based biomarkers in broader, non-selected populations outside of retrospective analyses and research cohorts still requires further investigation, including the combination with more effective neuropsychological assessments such as digital cognitive test solutions.

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Acknowledgments

R.P. is supported by the German Center for Neurodegenerative Disorders (Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE), the Deutsche Forschungsgemeinschaft (DFG, 1007 German Research Foundation) under Germany’s Excellence Strategy within the framework of 1008 the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the Davos Alzheimer’s Collaborative, the VERUM Foundation, the Robert-Vogel-Foundation, the National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre (NIHR203321), the University of Cambridge – Ludwig-Maximilians-University Munich Strategic Partnership within the framework of the German Excellence Initiative and Excellence Strategy, and the European Commission under the Innovative Health Initiative program (project 101132356).

Conflicts of Interest

R.P. has received honoraria for advisory boards and speaker engagements from Roche, EISAI, Eli Lilly, Biogen, Janssen-Cilag, Astra Zeneca, Schwabe, Grifols, Novo Nordisk, and Tabuk. J. W. has been an honorary speaker for Actelion, Amgen, Beeijing Yibai Science and Technology Ltd., Gloryren, Janssen Cilag, Med Update GmbH, Pfizer, and Roche Pharma and has been a member of the advisory boards of Abbott, Biogen, Boehringer Ingelheim, Lilly, MSD Sharp & Dohme, and Roche Pharma and receives fees as a consultant for Immungenetics, Noselab, and Roboscreen and holds the following patents: PCT/EP 2011 001724 and PCT/EP 2015 052945.

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Correspondence to Robert Perneczky .

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Perneczky, R. et al. (2024). Blood-Based Biomarkers for Early Alzheimer’s Disease Diagnosis in Real-World Settings. In: Perneczky, R. (eds) Biomarkers for Alzheimer’s Disease Drug Development. Methods in Molecular Biology, vol 2785. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3774-6_1

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  • DOI: https://doi.org/10.1007/978-1-0716-3774-6_1

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  • Publisher Name: Humana, New York, NY

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