title: Laser ablation-inductively coupled plasma-mass spectrometry imaging of white and gray matter iron distribution in Alzheimer's disease frontal cortex.
abstract: Iron deposition in the brain is a feature of normal aging, though in several neurodegenerative disorders, including Alzheimer's disease, the rate of iron accumulation is more advanced than in age-matched controls. Using laser ablation-inductively coupled plasma-mass spectrometry imaging we present here a pilot study that quantitatively assessed the iron content of white and gray matter in paraffin-embedded sections from the frontal cortex of Alzheimer's and control subjects. Using the phosphorus image as a confirmed proxy for the white/gray matter boundary, we found that increased intrusion of iron into gray matter occurs in the Alzheimer's brain compared to controls, which may be indicative of either a loss of iron homeostasis in this vulnerable brain region, or provide evidence of increased inflammatory processes as a response to chronic neurodegeneration. We also observed a trend of increasing iron within the white matter of the frontal cortex, potentially indicative of disrupted iron metabolism preceding loss of myelin integrity. Considering the known potential toxicity of excessive iron in the brain, our results provide supporting evidence for the continuous development of novel magnetic resonance imaging approaches for assessing white and gray matter iron accumulation in Alzheimer's disease.
authors.affiliation: Elemental Bio-imaging Facility, University of Technology Sydney, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia. Electronic address: dominic.hare@uts.edu.au.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University Medical Center, United States; Advanced Magnetic Resonance Imaging Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States.
authors.forename: Erika P
authors.initials: EP
authors.lastname: Raven
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Blaine R
authors.initials: BR
authors.lastname: Roberts
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Bogeski
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Portbury
authors.affiliation: Department of Anatomical Pathology, Alfred Hospital, Australia; Department of Medicine, Central Clinical School, Monash University, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State Hershey Medical Center, United States; Department of Neurosurgery, Penn State Hershey Medical Center, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: Department of Pathology, School of Biomedical Sciences, University of Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crouch
authors.affiliation: Elemental Bio-imaging Facility, University of Technology Sydney, Australia. Electronic address: philip.doble@uts.edu.au.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Doble
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D053685:Laser Therapy / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D010865:Pilot Projects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013054:Spectrophotometry, Atomic / Q000379:methods*; D014018:Tissue Distribution; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D007501:Iron