TY - JOUR

T1 - Plasma Aβ biomarker for early diagnosis and prognosis of Alzheimer's disease - a systematic review

AU - Ebbesen, Svend Ubbe

AU - Høgh, Peter

AU - Zibrandtsen, Ivan

N1 - Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

PY - 2023

Y1 - 2023

N2 - 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 (Aβ) as a biomarker of AD and explores the clinical implications of this line of research.METHODS: PubMed was searched using the keywords plasma Aβ 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 Aβ42/40 ratio, aPET and plasma Aβ42/40 ratio was conducted when possible.RESULTS: A total of 17 articles were identified. Plasma Aβ42/40 ratio was inversely correlated with aPET positivity r = -0.48 (95% confidence interval (CI): -0.65--0.31). In numerous studies, plasma Aβ42/40 ratio was also found to be directly correlated with CSF Aβ42 and CSF Aβ42/40 ratio r = 0.50 (95% CI: 0.30-0.69). Three studies found plasma Aβ42 to be positively associated with aPET positivity and CSF Aβ42; however, four other studies found no significant association between these variables. Seven studies reported no significant association of plasma Aβ40 with aPET or CSF Aβ40.CONCLUSION: Plasma Aβ42/40 ratio seems as a promising plasma biomarker as it significantly correlates inversely with aPET positivity and directly with CSF Aβ42 and CSF Aβ42/40 ratio. However, more research is warranted, including validation studies, longitudinally clinical studies, studies comparing measurement methods and studies of Aβ kinetics.

AB - 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 (Aβ) as a biomarker of AD and explores the clinical implications of this line of research.METHODS: PubMed was searched using the keywords plasma Aβ 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 Aβ42/40 ratio, aPET and plasma Aβ42/40 ratio was conducted when possible.RESULTS: A total of 17 articles were identified. Plasma Aβ42/40 ratio was inversely correlated with aPET positivity r = -0.48 (95% confidence interval (CI): -0.65--0.31). In numerous studies, plasma Aβ42/40 ratio was also found to be directly correlated with CSF Aβ42 and CSF Aβ42/40 ratio r = 0.50 (95% CI: 0.30-0.69). Three studies found plasma Aβ42 to be positively associated with aPET positivity and CSF Aβ42; however, four other studies found no significant association between these variables. Seven studies reported no significant association of plasma Aβ40 with aPET or CSF Aβ40.CONCLUSION: Plasma Aβ42/40 ratio seems as a promising plasma biomarker as it significantly correlates inversely with aPET positivity and directly with CSF Aβ42 and CSF Aβ42/40 ratio. However, more research is warranted, including validation studies, longitudinally clinical studies, studies comparing measurement methods and studies of Aβ kinetics.

KW - Humans

KW - Alzheimer Disease/diagnosis

KW - Amyloid beta-Peptides

KW - Prognosis

KW - Biomarkers

KW - Early Diagnosis

M3 - Review

C2 - 37341353

VL - 70

JO - Danish Medical Journal

JF - Danish Medical Journal

SN - 2245-1919

IS - 6

M1 - A07220446

ER -