Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease

• Published in: NeuroImage (Orlando, Fla.) Vol. 55; no. 1; pp. 32 - 38
• Main Authors: Leskovjan, Andreana C., Kretlow, Ariane, Lanzirotti, Antonio, Barrea, Raul, Vogt, Stefan, Miller, Lisa M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2011; Elsevier Limited
• Subjects: 60 APPLIED LIFE SCIENCES; Aging - metabolism; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid plaques; Animals; BRAIN; Brain - metabolism; COPPER; Cortex; DIAGNOSIS; Disease Models, Animal; DISEASES; DISTRIBUTION; Female; FLUORESCENCE; HIPPOCAMPUS; Humans; Imaging; IRON; Iron - metabolism; Laboratory animals; Male; Mice; Mice, Mutant Strains; MICROSCOPY; national synchrotron light source; Neuropathology; NMR; Nuclear magnetic resonance; PLAQUE FORMATION; Plaque, Amyloid - metabolism; SYMPTOMS; TARGETS; Tissue Distribution; Transgenic mice; X-ray fluorescence; ZINC; X-ray fluorescence; Imaging; Transgenic mice; Cortex; Iron; Copper; Alzheimer's disease; Amyloid plaques; Zinc; Hippocampus
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2010.11.073

Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the cortex and hippocampus using X-ray fluorescence microscopy (XFM). We found that iron in the cortex was 34% higher than age-matched controls at an early stage, corresponding to the commencement of plaque formation. The elevated iron was not associated with the amyloid plaques. Interestingly, none of the metal ions were elevated in the amyloid plaques until the latest time point (56weeks), where only the Zn content was significantly elevated by 38%. Since neuropathological changes in human Alzheimer's disease are presumed to occur years before the first cognitive symptoms appear, quantification of brain iron content could be a powerful marker for early diagnosis of Alzheimer's disease.
► Brain metal content is a potential target for early diagnosis and treatment of AD. ► In the PSAPP mouse, iron was elevated in the cortex at the onset of plaque formation. ► The elevated iron was not associated with the amyloid plaques. ► Iron, copper, and zinc were not elevated in PSAPP plaques at time points up to 56weeks. ► Only the zinc content was elevated at 56weeks, representing a marker of late-stage AD.