Amyloid plaques arise from zinc-enriched cortical layers in APP/PS1 transgenic mice and are paradoxically enlarged with dietary zinc deficiency.
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.
Stoltenberg
M
M
Neurobiology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark. ms@neuro.au.dk
Bush
A I
AI
Bach
G
G
Smidt
K
K
Larsen
A
A
Rungby
J
J
Lund
S
S
Doering
P
P
Danscher
G
G
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*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D015032:Zinc