Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker

Abstract

Cerebrospinal fluid and positron emission tomography biomarkers accurately predict an underlying Alzheimer's disease (AD) pathology; however, they represent either invasive or expensive diagnostic tools. Therefore, a blood-based biomarker like plasma amyloid beta (Aβ) that could correlate with the underlying AD pathology and serve as a prognostic biomarker or an AD screening strategy is urgently needed as a cost-effective and non-invasive diagnostic tool. In this paper we review the demographic, biologic, genetic and technical aspects that affect plasma Aβ levels. Findings of cross-sectional and longitudinal studies of plasma Aβ, including autosomal dominant AD cases, sporadic AD cases, Down syndrome cases and population studies, are also discussed. Finally, we review the association between cerebrovascular disease and Aβ plasma levels and the responses observed in clinical trials. Based on our review of the current literature on plasma Aβ, we conclude that further clinical research and assay development are needed before measures of plasma Aβ can be interpreted so they can be applied as trait, risk or state biomarkers for AD.

Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels

“…We then analyzed the correlations among plasma A β and other blood factors. In the ADNI cohort, platelet count, creatinine, and total protein affected plasma A β levels 18, 19. However, the IHPP cohort comprising a wide range of age did not report similar findings.…”

“…After adjusting for total protein, platelet count, and creatinine levels, which were previously reported as confounding factors for plasma A β levels,18, 19 the multiple linear regression model was used to clarify whether the age‐dependent increases in A β levels were affected by APOE‐ε4 . There were significant differences between carriers and noncarriers in regression lines of A β 42 ( P  < 0.0001) and A β 40/42 ( P  < 0.0001) but not A β 40 ( P  = 0.76) (Fig.…”

“…A β in plasma does not only originate in the brain because it is also involved in amyloid precursor protein (APP) metabolism in peripheral organs, it binds to several proteins and lipoproteins, is partially released from activated platelets, and is metabolized in the liver and cleared through the kidneys 19. However, a recent study suggested that 30–50% of plasma A β originates from the CNS 15…”

“…The gene dose of APOE‐ε4 may decrease plasma A β 42 levels with natural aging, or long‐term preclinical stage of AD dementia 10, 17. For this reason, basic information on how plasma A β levels are regulated over time by blood biochemical factors, cognitive function, and lifestyle remains to be clarified in order to adjust plasma A β levels for CNS amyloidosis‐specific markers 18, 19. Here, we analyzed definite factors of plasma A β of participants in The Iwaki Health Promotion Project (IHPP) in 2014, a community‐based annual health checkup study designed to prevent and improve lifestyle‐related diseases and quality of life.…”

Measurement of creatinine in human plasma using&nbsp;a functional porous polymer structure sensing motif

“…A series of experiments proved that Alzheimer's disease was closely associated with Plasma and their result showed that Alzheimer's can be detected from Plasma. [28][29][30][31] Another recent study by Yoshida et al 27 described that there was a slow increase of creatinine level in case of Alzheimer's disease as compared with normal blood. Figure 9 shows that creatinine levels in patients with Alzheimer's and healthy individuals were only slightly different, whereas in diabetic patients, this difference was extremely high (P0.05).…”