Modest amyloid deposition is associated with iron dysregulation, microglial activation and oxidative stress

DOI: 10.3233/JAD-2011-110614
PMID: 21971404

Authors: Joseph Gallagher (California Institute of Technology) , Mary Finnegan (University of Warwick) , Belinda Grehan (Trinity College Dublin) , Jon Dobson (Keele University) , Joanna Collingwood (University of Warwick) , Mariana Lynch (Trinity College Dublin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal of Alzheimer's Disease

State: Published (Approved)
Published: October 2011
Diamond Proposal Number(s): 1125

Abstract: There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from A?PP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid-?-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-?-containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology.

Journal Keywords: Iron; Alzheimer's Disease; Oxidative Stress

Subject Areas: Medicine, Biology and Bio-materials, Technique Development


Instruments: I18-Microfocus Spectroscopy