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Title: Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer's disease pathology.
Austin Authors: Ashraf, Azhaar;Ashton, Nicholas J;Chatterjee, Pratishtha;Goozee, Kathryn;Shen, Kaikai;Fripp, Jurgen;Ames, David;Rowe, Christopher C ;Masters, Colin L ;Villemagne, Victor L ;Hye, Abdul;Martins, Ralph N;So, Po-Wah
Affiliation: Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, 5, Cutcombe Road, Denmark Hill Campus, London, SE5 9RX, UK
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia
Australian E-Health Research Centre, CSIRO, Brisbane, Australia
Academic Unit for Psychiatry of Old Age, St. George's Hospital, University of Melbourne, Victoria, VIC, Australia
National Ageing Research Institute, Parkville, VIC, Australia
The Florey Institute, University of Melbourne, Parkville, VIC, Australia
Molecular Imaging and Therapy
Rapiscan Systems, St Leonards, Sydney, Australia
Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, King's College London, London, UK
NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
School of Medical Sciences, Edith Cowan University, 270, Joondalup, WA, 6027, Australia
KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, 2109, Australia
Clinical Research Department, Anglicare, Sydney, NSW, Australia
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, 5, Cutcombe Road, Denmark Hill Campus, London, SE5 9RX, UK
Issue Date: 9-Jun-2020
Date: 2020-06-09
Publication information: Alzheimer's Research & Therapy 2020; 12(1): 72
Abstract: 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. 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. 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. 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.
DOI: 10.1186/s13195-020-00634-1
ORCID: 0000-0003-3449-8532
Journal: Alzheimer's Research & Therapy
PubMed URL: 32517787
Type: Journal Article
Subjects: Alzheimer’s disease
Cognitive impairment
Cognitively normal
Mild cognitive impairment
Appears in Collections:Journal articles

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