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

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 between APP and the iron-bound form of Lf secreted from activated microglia diverted neuronal APP endo

SUBMITTER: Tsatsanis A 

PROVIDER: S-EPMC8758478 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature