The acute phase protein lactoferrin is a key feature of Alzheimer’s disease and predictor of Aβ burden through induction of APP amyloidogenic processing

A Tsatsanis; AN McCorkindale; BX Wong; E Patrick; TM Ryan; RW Evans; AI Bush; GT Sutherland; A Sivaprasadarao; B Guennewig; JA Duce

Journal article

The acute phase protein lactoferrin is a key feature of Alzheimer’s disease and predictor of Aβ burden through induction of APP amyloidogenic processing

A Tsatsanis, AN McCorkindale, BX Wong, E Patrick, TM Ryan, RW Evans, AI Bush, GT Sutherland, A Sivaprasadarao, B Guennewig, JA Duce

Molecular Psychiatry | SPRINGERNATURE | Published : 2021

DOI: 10.1038/s41380-021-01248-1

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Abstract

Amyloidogenic processing of the amyloid precursor protein (APP) forms the amyloid-β peptide (Aβ) component of pathognomonic extracellular plaques of AD. Additional early cortical changes in AD include neuroinflammation and elevated iron levels. Activation of the innate immune system in the brain is a neuroprotective response to infection; however, persistent neuroinflammation is linked to AD neuropathology by uncertain mechanisms. Non-parametric machine learning analysis on transcriptomic data from a large neuropathologically characterised patient cohort revealed the acute phase protein lactoferrin (Lf) as the key predictor of amyloid pathology. In vitro studies showed that an interaction be..

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University of Melbourne Researchers

Bruce Wong Author

Ashley Bush Author

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Grants

Awarded by Alzheimer’s Society

Funding Acknowledgements

The authors would like to thank Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago for making their data available. Their data collection was supported through funding by NIA grants: P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, the Illinois Department of Public Health and the Translational Genomics Research Institute. Work carried out was supported by Alzheimer's Society UK, the European Research Council and Australian National Health & Medical Research Council (NHMRC) (#1061587, #1163249, #1037746 and #1095127). These bodies had no role in the design and interpretation of the study or writing of the manuscript.