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

Alzheimer’s Research & Therapy

AIBL¹  David Ames²  Kaikai Shen³  Victor Villemagne⁴  Christopher Rowe⁴  Azhaar Ashraf⁵  Po-Wah So⁵  Abdul Hye⁶  Nicholas J. Ashton⁶  Kathryn Goozee⁷  Jurgen Fripp⁸  Pratishtha Chatterjee⁹  Ralph N. Martins⁹  Colin L. Masters^1,10 

[1] ;Academic Unit for Psychiatry of Old Age, St. George’s Hospital, University of Melbourne;Australian E-Health Research Centre, CSIRO;Department of Molecular Imaging and Therapy, Austin Health;Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London;Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, King’s College London;KaRa Institute of Neurological Diseases;Rapiscan Systems;School of Medical Sciences, Edith Cowan University;The Florey Institute, University of Melbourne;

关键词: Alzheimer’s disease;    Cognitively normal;    Cognitive impairment;    Heme;    Hemoglobin;    Iron;   

DOI  :  10.1186/s13195-020-00634-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown