title: Amyloid plaques arise from zinc-enriched cortical layers in APP/PS1 transgenic mice and are paradoxically enlarged with dietary zinc deficiency.
abstract: The ZnT3 zinc transporter is uniquely expressed in cortical glutamatergic synapses where it organizes zinc release into the synaptic cleft and mediates beta-amyloid deposition in transgenic mice. We studied the association of zinc in plaques in relation to cytoarchitectural zinc localization in the APP/PS1 transgenic mouse model of Alzheimer's disease. The effects of low dietary zinc for 3 months upon brain pathology were also studied. We determined that synaptic zinc distribution within cortical layers is paralleled by amyloid burden, which is heaviest for both in layers 2-3 and 5. ZnT3 immunoreactivity is prominent in dystrophic neurites within amyloid plaques. Low dietary zinc caused a significant 25% increase in total plaque volume in Alzheimer's mice using stereological measures. The level of oxidized proteins in brain tissue did not changed in animals on a zinc-deficient diet compared with controls. No obvious changes were observed in the autometallographic pattern of zinc-enriched terminals in the neocortex or in the expression levels of zinc transporters, zinc importers or metallothioneins. A small decrease in plasma zinc induced by the low-zinc diet was consistent with the subclinical zinc deficiency that is common in older human populations. While the mechanism remains uncertain, our findings indicate that subclinical zinc deficiency may be a risk factor for Alzheimer's pathology.
authors.affiliation: Neurobiology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark. ms@neuro.au.dk
authors.forename: M
authors.initials: M
authors.lastname: Stoltenberg
authors.forename: A I
authors.initials: AI
authors.lastname: Bush
authors.forename: G
authors.initials: G
authors.lastname: Bach
authors.forename: K
authors.initials: K
authors.lastname: Smidt
authors.forename: A
authors.initials: A
authors.lastname: Larsen
authors.forename: J
authors.initials: J
authors.lastname: Rungby
authors.forename: S
authors.initials: S
authors.lastname: Lund
authors.forename: P
authors.initials: P
authors.lastname: Doering
authors.forename: G
authors.initials: G
authors.lastname: Danscher
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005526:Food, Formulated; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009751:Nutritional Requirements; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics; D012307:Risk Factors; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D015032:Zinc