Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: a focused review on recent advances
- 11 September 2021
- journal article
- review article
- Published by BMJ in Journal of Neurology, Neurosurgery & Psychiatry
- Vol. 92 (11), 1231-1241
- https://doi.org/10.1136/jnnp-2021-327370
Abstract
Discovery and development of clinically useful biomarkers for Alzheimer’s disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau (P-tau). More recently, however, emerging technologies with superior sensitivity and specificity for measuring Aβ and P-tau have reported high concordances with AD severity. In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish Aβ and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of Aβ peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.Keywords
Funding Information
- National Medical Research Council (NMRC/CSA-SI/007/2016)
This publication has 85 references indexed in Scilit:
- Plasma Aβ but Not Tau is Related to Brain PiB Retention in Early Alzheimer’s DiseaseACS Chemical Neuroscience, 2014
- The amyloid-β degradation pattern in plasma—A possible tool for clinical trials in Alzheimer's diseaseNeuroscience Letters, 2014
- Combined Plasma Biomarkers for Diagnosing Mild Cognition Impairment and Alzheimer’s DiseaseACS Chemical Neuroscience, 2013
- Brain amyloid-β oligomers in ageing and Alzheimer’s diseaseBrain, 2013
- Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarkerAlzheimer's Research & Therapy, 2013
- Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in HumansPLOS ONE, 2011
- Soluble Aβ oligomer production and toxicityJournal of Neurochemistry, 2011
- Evaluation of plasma Aβ40 and Aβ42 as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairmentNeurobiology of Aging, 2010
- Amyloid oligomers: formation and toxicity of Aβ oligomersThe FEBS Journal, 2010
- Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascadeThe Lancet Neurology, 2010