Blood-based high sensitivity measurements of beta- amyloid and phosphorylated...

chenyaoxin

                                                                                                                                                                                                                       

Discoveryand development of clinically useful biomarkers for Alzheimer’s disease (AD)and related dementias havebeen the focus of recent research efforts. While cerebrospinal fluid andpositron emission tomography or MRI-based neuroimaging markers have made the invivo detection of AD pathology and its consequences possible, the high cost andinvasiveness have limited their widespread use in the clinical setting. On theother hand, advances in potentially more accessible blood-based biomarkers hadbeen impeded by lack of sensitivity in detecting changes in markers of thehallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau(P-tau). More recently, however, emerging technologies with superiorsensitivity and specificity formeasuring Aβ and P-tau have reported high concordances with AD severity. Inthis focused review, we describe several emerging technologies, includingimmunoprecipitation-mass spectrometry (IP-MS), single molecule array and MesoScale Discovery immunoassay platforms, and appraise the current literaturearising from their use to identify plaques, tangles and other AD-associatedpathology. While there is potential clinical utility in adopting thesetechnologies, we also highlight the further studies needed to establish Aβ andP-tau as blood-based biomarkers for AD, including validation with existinglarge sample sets, new independent cohorts from diverse backgrounds as well aspopulation-based longitudinal studies. In conclusion, the availability ofsensitive and reliable measurements of Aβ peptides and P-tau species in bloodholds promise for the diagnosis, prognosis and outcome assessments in clinicaltrials for AD.