Biological Marker Candidates of Alzheimer's Disease in Blood, Plasma, and Serum

Abstract

At the earliest clinical stages of Alzheimer's disease (AD), when first symptoms are mild, making a reliable and accurate diagnosis is difficult. AD related brain pathology and underlying molecular mechanisms precede symptoms. Biological markers can serve as supportive early screening and diagnostic tools as well as indicators of presymptomatic biochemical change. Moreover, biomarkers cover a variety of roles and functions such as disease prediction, indicating disease acuity and progression, and may ensure biological mapping of treatment outcome. Early screening, detection, and diagnosis of AD would permit earlier disease modifying intervention at potentially reversible stages. To date, most established biological markers from both cerebrospinal fluid neurochemistry and structural and functional neuroimaging have not reached widespread clinical application. Crucial remaining problems, such as easy acceptance and application of a test, cost-effectiveness, and noninvasiveness, need to be resolved. The development and validation of precise, reliable, and robust tests and biomarkers in blood, plasma, or serum has therefore been for a long time the ultimate focus of many research groups worldwide. Blood-based testing will most likely be the prerequisite to future sensitive screening of large populations at risk of AD and the baseline in a diagnostic flow approach to AD. The status and emerging perspectives on hypothesis and exploratory-based candidate biomarkers derived from blood, plasma, and serum are reviewed and discussed.

A Blood-Based, 7-Metabolite Signature for the Early Diagnosis of Alzheimer's Disease

“…However, the invasive nature of CSF sample collection limits the clinical utility of these markers; CSF can only be collected by lumbar puncture, which can be particularly difficult to perform in elderly patients and precludes the collection of multiple samples over time. Neuroimaging approaches such as structural and functional magnetic resonance imaging (MRI), amyloid tracer imaging, and positron emission tomography (PET), are also effective prognostic tools, but are expensive and often difficult to implement in routine settings [11,12]. Faced with a growing elderly population, current CSF and neuroimaging techniques are not ideal first-line approaches for screening large numbers of candidate AD patients.…”

A Blood-Based Algorithm for the Detection of Alzheimer’s Disease

“…rural elders, ethnic minorities), which limits their usefulness as screeners for AD. A blood-based test, however, would provide a rapid cost-effective means of screening for AD at the population level, broadening access to care globally [2,3]. As part of a multi-stage process, such a blood test would provide an optimal initial screening tool that could be followed up by advanced clinical, neuroimaging, and/or CSF analyses [3] for screen-positive cases.…”

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

“…Recently, a new sandwich ELISA for p-tau231P detection in serum was developed. However, reliable data regarding its use for AD diagnosis is still lacking [72] . Studies, instead, have been concentrated on protein kinases and phosphatases, whose alterations are associated with tau pathology.…”