Plasma A biomarker for early diagnosis and prognosis of Alzheimer' s disease - a systematic review

INTRODUCTION. Alzheimer's disease (AD) is the most common cause of dementia worldwide and a cost-effective diagnostic biomarker is needed. This systematic review provides an overview of the current research on plasma amyloid beta (A beta) as a biomarker of AD and explores the clinical implications of this line of research. METHODS. PubMed was searched using the keywords plasma A beta and AD from 2017 to 2021. Only clinical studies involving amyloid PET (aPET) or cerebrospinal fluid (CSF) biomarker analysis (or both) were included. A meta-analysis of CSF A beta 42/40 ratio, aPET and plasma A beta 42/40 ratio was conducted when possible. RESULTS. A total of 17 articles were identified. Plasma A beta 42/40 ratio was inversely correlated with aPET positivity r = -0.48 (95% confidence interval (CI): -0.65--0.31). In numerous studies, plasma A beta 42/40 ratio was also found to be directly correlated with CSF A beta 42 and CSF A beta 42/40 ratio r = 0.50 (95% CI: 0.30-0.69). Three studies found plasma A beta 42 to be positively associated with aPET positivity and CSF A beta 42; however, four other studies found no significant association between these variables. Seven studies reported no significant association of plasma A beta 40 with aPET or CSF A beta 40. CONCLUSION. Plasma A beta 42/40 ratio seems as a promising plasma biomarker as it significantly correlates inversely with aPET positivity and directly with CSF A beta 42 and CSF A beta 42/40 ratio. However, more research is warranted, including validation studies, longitudinally clinical studies, studies comparing measurement methods and studies of A beta kinetics.