Plasma biomarkers for Alzheimer's and related dementias: A review and outlook for clinical neuropsychology

Recent technological advances have improved the sensitivity and specificity of blood-based biomarkers for Alzheimer's disease and related dementias. Accurate quantification of amyloid-ss peptide, phosphorylated tau (pTau) isoforms, as well as markers of neurodegeneration (neurofilament light chain [NfL]) and neuro-immune activation (glial fibrillary acidic protein [GFAP] and chitinase-3-like protein 1 [YKL-40]) in blood has allowed researchers to characterize neurobiological processes at scale in a cost-effective and minimally invasive manner. Although currently used primarily for research purposes, these blood-based biomarkers have the potential to be highly impactful in the clinical setting - aiding in diagnosis, predicting disease risk, and monitoring disease progression. Whereas plasma NfL has shown promise as a non-specific marker of neuronal injury, plasma pTau181, pTau217, pTau231, and GFAP have demonstrated desirable levels of sensitivity and specificity for identification of individuals with Alzheimer's disease pathology and Alzheimer's dementia. In this forward looking review, we (i) provide an overview of the most commonly used blood-based biomarkers for Alzheimer's disease and related dementias, (ii) discuss how comorbid medical conditions, demographic, and genetic factors can inform the interpretation of these biomarkers, (iii) describe ongoing efforts to move blood-based biomarkers into the clinic, and (iv) highlight the central role that clinical neuropsychologists may play in contextualizing and communicating blood-based biomarker results for patients.