Charles Shieh-Yueh Yang - Böcker

Diagnosing Alzheimer’s disease (AD) and other neurodegenerative diseases such as dementia with Lewy bodies (DLB), Parkinson’s disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis poses significant challenges to healthcare, often resulting in delayed or inadequate patient care.  Additionally many of the conditions have overlapping phenotypes or pathologies which makes it difficult to identify single pathological contributions.Despite the high prevalence of mild cognitive impairment and dementia and other neurodegenerative diseases, up to 92% of patients with early cognitive decline remain undiagnosed or misdiagnosed in healthcare settings. Moreover, the scarcity of neurological specialists in the US exacerbates the situation, with many patients failing to access specialty care, and those who are referred experience prolonged wait times. Consequently, because the majority of AD neuroimaging or cerebrospinal fluid (CSF) biomarker testing takes place in specialty care settings (i.e., secondary or tertiary care), only a small fraction of patients with cognitive impairment receives such testing.Traditional biomarker modalities for confirming neuro pathology in conditions such as AD, PD, DLB and FTD include positron emission tomography (PET) or a lumbar puncture to collect CSF to measure concentrations of A, tau and others. PET and CSF biomarkers have a number of shortcomings including high cost, limited accessibility, and perceived invasiveness, making them unsuitable for widespread use across care settings. Recent advancements in blood-based biomarker (BBM) tests for AD offer a promising alternative. These tests are less costly, more accessible, more acceptable to patients, and more practical for serial collection to monitor disease progression.In PD and DLB, there are emerging CSF assays for alpha-synuclein but a BBBM for PD or DLB has not emerged.  There are BBBMs being considered for FTD and PSP but none have been commercially approved.Blood-based biomarkers (BBM) for Alzheimer’s disease (AD) and other neurodegenerative diseases are being increasingly used in clinical practice to support clinical diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments that require confirmation of amyloid pathology. The major change in the field is that the detection assays have improved from nanomolar (10-9) to femtomolar (10-15) which allows for detection of proteins previously not considered measurable in the blood spaces.The clinical integration of blood-based biomarkers (BBBMs) for AD and other neurodegenerative diseases holds promise in enabling early detection of pathology and timely intervention. Similar investigations are being considered for other neurodegenerative diseases. However, several critical considerations, such as limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and how individual test parameters performed on different assay platforms can be meaningfully compared.This book summarizes the current assays ready for clinical use or in development for neurodegenerative diseases including AD, PD, DLB, PSP, FTD and ALS, from assay technologies to clinical applications. As starting from technologies in Chapter 1, seventeen ultra-sensitive assay platforms are introduced. The details of detecting mechanism, feature of assay, plasma preparation, commercialization, and key specifications of assay kits are illustrated for each assay platform. Readers can have comprehensive understanding about insights of these complicated technologies for assaying blood-based biomarkers associated with neurodegenerative diseases. Owing to the ultralow concentrated biomarkers in human blood, the sample (plasma) preparations significantly attribute to the measured results. In Chapter 2, the effects of factors of plasma preparations on the measurements are explored. The recipes include blood collecting tubes, storage temperature of whole blood, centrifugation temperatures of whole blood, time period to centrifuge blood samples from blood draw, lifetime of biomarkers in frozen plasma, and freeze/thaw cycles of plasma. The contents are really helpful for developers, laboratory technicians and physicians to establish the standard operating processes for plasma preparations in assaying blood-based biomarkers of neurodegenerative diseases. The assay kits and analyzers of blood-based biomarkers for assessing/diagnosing neurodegenerative diseases are categorized to in-vitro diagnosis (IVD) medical devices. Many bench tests must be conducted to demonstrate the safety, pre-clinical performance and validity of measurements. In Chapter 3, the philosophy, guidelines and methods of the bench tests for assay kits and analyzers measuring blood-based biomarkers are literature. Practical examples are given to illustrate the details of bench tests for characterizing the assay kits and analyzers under developments. In Chapter 4, the clinical validations of blood-based biomarker tests for assessing/diagnosing neurodegenerative disease are reviewed. The criteria are to correlate blood-based biomarker tests to standard diagnosis in guidelines for neurodegenerative disease, such as brain tissue staining, neuroimaging, biomarker tests in cerebrospinal fluid, clinical diagnosis, etc., depending on the types of neurodegenerative disease. The contents can help readers bridge blood-based biomarkers to the standard diagnosis. Authors have been using blood-based biomarkers in routine practice for many years. Valuable experiences in solving clinical puzzles using blood-based biomarkers are shared in Chapter 5. Examples are given in this chapter to help readers to learn when blood-based biomarker tests are needed for clients, what kinds of biomarkers should be measured, and how the test results are correctly interpreted. The contents also layout the prospectives and challenges of blood-based biomarkers in real-world practice.