Document Type

Journal Article

Publication Title

Alzheimer's Research and Therapy


Springer Nature


School of Medical and Health Sciences




Ashraf, A., Ashton, N. J., Chatterjee, P., Goozee, K., Shen, K., Fripp, J., ... & Hye, A. (2020). Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology. Alzheimer's Research & Therapy, 12(1), 1-13.


Background:Heme and iron homeostasis is perturbed in Alzheimer’s disease (AD); therefore, the aim of the studywas 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 FlagshipStudy 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 relativeprotein abundances in plasma samples from 144 CN individuals from the AIBL and 94 CN from KARVIAH cohorts and21 MCI and 25 AD from AIBL cohort. ANCOVA models were utilized to assess the differences in plasma proteinsimplicated in heme/iron metabolism, while multiple regression modeling (and partial correlation) was performed toexamine the association between heme and iron proteins, structural neuroimaging, and cognitive measures.Results:Of the plasma proteins implicated in iron and heme metabolism, hemoglobin subunitβ(p= 0.001) was significantlyincreased in AD compared to CN individuals. Multiple regression modeling adjusted for age, sex, APOEε4 genotype, anddisease status in the AIBL cohort revealed lower levels of transferrin but higher levels of hemopexin associated with augmentedbrain 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 associationsbetween 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 betweenheme/iron metabolism and AD warrants further investigation.



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This work is licensed under a Creative Commons Attribution 4.0 License.