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

Alzheimer Disease / genetics Amyloid beta-Peptides Australia Cognitive Dysfunction Hemopexin Humans Proteomics Transferrin
Alzheimer’s disease Cognitive impairment Cognitively normal Heme Hemoglobin Iron Mild cognitive impairment Proteomics Transferrin

Journal

Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643

Informations de publication

Date de publication:
09 06 2020
Historique:
received: 05 03 2020
accepted: 18 05 2020
entrez: 11 6 2020
pubmed: 11 6 2020
medline: 25 6 2021
Statut: epublish

Résumé

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.

Sections du résumé

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.

Identifiants

DOI: 10.1186/s13195-020-00634-1 PMID: 32517787 PMC: PMC7285604
pubmed: 32517787
doi: 10.1186/s13195-020-00634-1
pii: 10.1186/s13195-020-00634-1
pmc: PMC7285604
doi:

Substances chimiques

Amyloid beta-Peptides 0
Transferrin 0
Hemopexin 9013-71-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

72

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom

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Auteurs

Azhaar Ashraf (A)

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.

Nicholas J Ashton (NJ)

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.

Pratishtha Chatterjee (P)

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.

Kathryn Goozee (K)

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.
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia.

Kaikai Shen (K)

Australian E-Health Research Centre, CSIRO, Brisbane, Australia.
Rapiscan Systems, St Leonards, Sydney, Australia.

Jurgen Fripp (J)

Rapiscan Systems, St Leonards, Sydney, Australia.

David Ames (D)

Academic Unit for Psychiatry of Old Age, St. George's Hospital, University of Melbourne, Victoria, VIC, Australia.
National Ageing Research Institute, Parkville, VIC, Australia.

Christopher Rowe (C)

Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC, Australia.

Colin L Masters (CL)

The Florey Institute, University of Melbourne, Parkville, VIC, Australia.

Victor Villemagne (V)

Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC, Australia.

Abdul Hye (A)

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.

Ralph N Martins (RN)

School of Medical Sciences, Edith Cowan University, 270, Joondalup, WA, 6027, Australia. ralph.martins@mq.edu.au.
KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia. ralph.martins@mq.edu.au.
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, 2109, Australia. ralph.martins@mq.edu.au.

Po-Wah So (PW)

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. po-wah.so@kcl.ac.uk.
ORCID: 0000-0003-3449-8532

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Régions géographiques › Océanie › Australasie › Australie › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Glycoprotéines › Hémopexine › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Plasma transferrin and hemopexin are...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Transferrines › Transferrine › Plasma transferrin and hemopexin are...