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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2020

Open Access 01-12-2020 | Alzheimer's Disease | Research

Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology

Authors: Azhaar Ashraf, Nicholas J. Ashton, Pratishtha Chatterjee, Kathryn Goozee, Kaikai Shen, Jurgen Fripp, David Ames, Christopher Rowe, Colin L. Masters, Victor Villemagne, Abdul Hye, Ralph N. Martins, Po-Wah So, AIBL

Published in: Alzheimer's Research & Therapy | Issue 1/2020

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Abstract

Background

Heme and iron homeostasis is perturbed in Alzheimer’s disease (AD); therefore, the aim of the study was to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN), mild cognitive impairment (MCI), and AD individuals from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohorts.

Methods

Non-targeted proteomic analysis by high-resolution mass spectrometry was performed to quantify relative protein abundances in plasma samples from 144 CN individuals from the AIBL and 94 CN from KARVIAH cohorts and 21 MCI and 25 AD from AIBL cohort. ANCOVA models were utilized to assess the differences in plasma proteins implicated in heme/iron metabolism, while multiple regression modeling (and partial correlation) was performed to examine the association between heme and iron proteins, structural neuroimaging, and cognitive measures.

Results

Of the plasma proteins implicated in iron and heme metabolism, hemoglobin subunit β (p = 0.001) was significantly increased in AD compared to CN individuals. Multiple regression modeling adjusted for age, sex, APOEε4 genotype, and disease status in the AIBL cohort revealed lower levels of transferrin but higher levels of hemopexin associated with augmented brain amyloid deposition. Meanwhile, transferrin was positively associated with hippocampal volume and MMSE performance, and hemopexin was negatively associated with CDR scores. Partial correlation analysis revealed lack of significant associations between heme/iron proteins in the CN individuals progressing to cognitive impairment.

Conclusions

In conclusion, heme and iron dyshomeostasis appears to be a feature of AD. The causal relationship between heme/iron metabolism and AD warrants further investigation.
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Metadata
Title
Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology
Authors
Azhaar Ashraf
Nicholas J. Ashton
Pratishtha Chatterjee
Kathryn Goozee
Kaikai Shen
Jurgen Fripp
David Ames
Christopher Rowe
Colin L. Masters
Victor Villemagne
Abdul Hye
Ralph N. Martins
Po-Wah So
AIBL
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2020
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-020-00634-1

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