Affiliations: [a] Neurosurgery Center for Research, Training and Education, Loma Linda University, Loma Linda, CA, USA | [b] Molecular Radiation Biology Laboratories, Loma Linda University, Loma Linda, CA, USA | [c] Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA | [d] Department of Chemistry and the Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA, USA
Correspondence:
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Correspondence to: Wolff Kirsch, Neurosurgery Center for Research, Training and Education, Loma Linda University, 11175 Campus Dr, Coleman Pavilion, Suite 11113, Loma Linda, California, USA. Tel.: +1 909 558 7070; E-mail: [email protected].
Abstract: Cerebral amyloid angiopathy (CAA) is a vascular lesion associated with Alzheimer's disease (AD) present in up to 95% of AD patients and produces MRI-detectable microbleeds in many of these patients. It is possible that CAA-related microbleeding is a source of pathological iron in the AD brain. Because the homeostasis of copper, iron, and zinc are so intimately linked, we determined whether CAA contributes to changes in the brain levels of these metals. We obtained brain tissue from AD patients with severe CAA to compare to AD patients without evidence of vascular amyloid-β. Patients with severe CAA had significantly higher non-heme iron levels. Histologically, iron was deposited in the walls of large CAA-affected vessels. Zinc levels were significantly elevated in grey matter in both the CAA and non-CAA AD tissue, but no vascular staining was noted in CAA cases. Copper levels were decreased in both CAA and non-CAA AD tissues and copper was found to be prominently deposited on the vasculature in CAA. Together, these findings demonstrate that CAA is a significant variable affecting transition metals in AD.
Keywords: Atomic absorption, coppersensor 1 (CS1), ferrous, non-heme iron
