title: Effect of cerebral amyloid angiopathy on brain iron, copper, and zinc in Alzheimer's disease.
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.
authors.affiliation: Neurosurgery Center for Research, Training and Education, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schrag
authors.forename: Andrew
authors.initials: A
authors.lastname: Crofton
authors.forename: Matthew
authors.initials: M
authors.lastname: Zabel
authors.forename: Arshad
authors.initials: A
authors.lastname: Jiffry
authors.forename: David
authors.initials: D
authors.lastname: Kirsch
authors.forename: April
authors.initials: A
authors.lastname: Dickson
authors.forename: Xiao Wen
authors.initials: XW
authors.lastname: Mao
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Dylan W
authors.initials: DW
authors.lastname: Domaille
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang
authors.forename: Wolff
authors.initials: W
authors.lastname: Kirsch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism* / Q000473:pathology; D003300:Copper / Q000378:metabolism*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015032:Zinc / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D003300:Copper; D007501:Iron; D015032:Zinc