Open AccessBlood‐based biomarkers for Alzheimer's disease and related dementias: Keys to success and things to consider
Author(s) -
Zetterberg Henrik,
Apostolova Liana G.,
Snyder Peter J.
Publication year - 2019
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1016/j.dadm.2019.10.001
Subject(s) - dementia , biomarker , medicine , cerebrospinal fluid , disease , alzheimer's disease , cognitive decline , neuroscience , bioinformatics , pathology , psychology , biology , biochemistry
During the last two decades, considerable progress has been made in the field of fluid and imaging biomarkers for neurodegenerative dementias. As a result, the most recent research and clinical guidelines (the National Institute on Aging and Alzheimer’s Association, International Working Group 2, National Institute for Health and Care Excellence) incorporate cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers in the diagnostic criteria of dementia and mild cognitive impairment due to Alzheimer’s disease (AD) [1–3]. However, as both CSF and amyloid PET examinations require expert knowledge and are of limited availability outside specialized memory clinics, there is no doubt that blood tests would be much easier to implement in clinical medicine and as screening tools when recruiting patients for clinical trials. However, there are several issues, both biological and technical, with the measurement of biomarkers for neurodegenerative dementias in blood. First, a biomarker that has its origin in the central nervous system (CNS) has to cross the blood-brain barrier to be detected in the periphery, and if the concentration in CSF is low, it will be even lower in the blood. Second, if the biomarker is not specific for the CNS but also expressed in peripheral tissues, the contribution from the CNS will potentially be hard to detect, given the high biological background caused by non-CNS sources. Third, the broad dynamic range of the plasma proteome, which is dominated by plasma proteins, such as albumin and immunoglobulins, with only minute amounts of CNSderived proteins, presents an analytical challenge [4]. Fourth, heterophilic antibodies may be present in blood, which may interfere in immunoassays [5]. Fifth, the analyte of interest may undergo proteolytic degradation by various proteases in plasma [6]. Sixth, clearance of the biomarker by the liver or the kidneys, diurnal variation, and plasma volume changes may introduce significant variability.