Plasma A\u03b2 analysis using magnetically-labeled immunoassays and PET 18F-florbetapir binding in non-demented patients with major depressive disorder

Kuan-Yi Wu,Kun-Ju Lin,Tzu-Chen Yen,Chia-Yih Liu,Sheng-Yao Huang,Ing-Tsung Hsiao,Chia-Hsiang Chen,Jung-Lung Hsu

doi:10.1038/s41598-018-21140-3

Kuan-Yi Wu, Kun-Ju Lin + Show 6 more

Open Access

https://doi.org/10.1038/s41598-018-21140-3

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Abstract

An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer’s disease (AD); however, the usefulness of plasma Aβ levels are not well-established. This study investigated the relationships between plasma Aβ levels and cerebral amyloidosis in 36 non-demented patients with major depressive disorder (MDD). All participants underwent 18F-florbetapir PET imaging and provided a blood sample at the same time for immunomagnetic reduction assay to measure the plasma levels of Aβ40 and Aβ42. We found inverse associations of the plasma Aβ42 level and the Aβ42/Aβ40 ratio, and a positive association of the plasma Aβ40 level, with cerebral amyloid deposition in the precuneus, parietal and posterior cingulate cortex. Subgroup analyses in subjects with higher 18F-florbetapir uptake values or MDD with amnestic mild cognitive impairment revealed more pervasive relationships of plasma Aβ measures with 18F-florbetapir binding across the brain regions examined. The study suggested that regional brain amyloid deposition in terms of 18F-florbetapir PET uptake had weak-to-moderate associations with plasma Aβ42 and Aβ40 levels, and the Aβ42/Aβ40 ratio. Validation in a larger population of subjects of known cerebral amyloidosis status is needed. Careful interpretation of plasma data is warranted.

Highlights

An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer’s disease (AD); the usefulness of plasma Aβ levels are not well-established
Plasma Aβ42/Aβ40 r p positive (Aβ40) ratio was regarded as a promising biomarker compared to individual Aβ peptide because the plasma Aβ42 level would decline as selective brain Aβ42 deposition occurs initially, and this would make the Aβ42/Aβ40 ratio fall into the lower value[11]
Neither the plasma Aβ42 level, Aβ40 level or Aβ42/ Aβ40 ratio was related to age, sex or educational level, with the exception that the plasma Aβ42 level was negatively correlated with age (r = −0.419, p = 0.011)

Summary

Introduction

An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer’s disease (AD); the usefulness of plasma Aβ levels are not well-established. The study suggested that regional brain amyloid deposition in terms of 18F-florbetapir PET uptake had weak-to-moderate associations with plasma Aβ42 and Aβ40 levels, and the Aβ42/Aβ40 ratio. Growth of insight into pathogenic events and the course of AD has led to the establishment of new research and diagnostic criteria[1] These criteria were recently developed by the International Working Group (IWG)[2,3] and the task force of the National Institute on Aging and the Alzheimer Association (NIA-AA)[4], mainly for research purposes. Plasma Aβ proteins have not been proven to be reliable and useful biomarkers to date

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