title: Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease.
abstract: Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.
authors.affiliation: Department of Radiology, Lucas Center for Imaging, Stanford University, Stanford, CA, USA. Electronic address: mzeineh@stanford.edu.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Zeineh
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neuroradiology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Hagen H
authors.initials: HH
authors.lastname: Kitzler
authors.affiliation: Department of Pathology and Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Hammond
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Department of Radiology, Lucas Center for Imaging, Stanford University, Stanford, CA, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Rutt
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D011180:Postmortem Changes; D011956:Receptors, Cell Surface / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D000682:Amyloid; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D016875:tau Proteins; D007501:Iron; D000110:Acetylcholinesterase
keywords: Alzheimer; Amyloid; Hippocampus; Iron; MRI; Microglia