Alteration of the Cerebral Zinc Pool in a Mouse Model of Alzheimer Disease

作者：Lee Joo Yong^*; Cho Eunsil; Seo Jung Woo; Hwang Jung Jin; Koh Jae Young

来源：Journal of Neuropathology and Experimental Neurology, 2012, 71(3): 211-222.

DOI：10.1097/NEN.0b013e3182417387

• Alzheimer disease
• Amyloid beta
• Amyloidopathy
• Amyloid plaques
• Dystrophic neurites
• Synaptic vesicles
• Zinc transporter

Synaptic vesicle Zn2+ is regulated by zinc transporter 3 (ZnT3) and is involved in neurotransmission and synaptic plasticity. Here, we describe extensive alterations of ZnT3-regulated Zn2+ pools in the brains of human amyloid precursor protein-transgenic (Tg2576) mice. In contrast to wild-type littermates in which ZnT3 expression and synaptic Zn2+ increased with age, there were age-dependent reductions in ZnT3 expression and synaptic Zn2+ levels in the hippocampal mossy fiber area of Tg2576 mice. In these mice, a novel Zn2+ pool and ZnT3 expression were colocalized and appeared along dystrophic neurites surrounding compact amyloid plaques that were identified by in situ blue fluorescence, congophilic birefringence, and A beta 42 immunoreactivity. Zn2+-specific histofluorescence and ZnT3 immunofluorescence in dystrophic neurites were also colocalized with the delta-subunit of adaptor protein complex 3, lysosome-associated membrane protein, cathepsin D, and neurofilament-containing hyperphosphorylated paired helical filaments. The synaptic vesicle marker protein synaptophysin and vesicle-associated membrane protein were not found in these neurites, suggesting a role of ZnT3 distinct from its normal role in synaptic Zn2+. ZnT3 immunoreactivity and Zn2+ histofluorescence were also evident in activated astrocytes. These data suggest that extensive modifications of the cerebral Zn2+ pool, particularly synaptic Zn2+, may underlie neuronal dysfunction characteristic of Alzheimer disease.

• 出版日期2012-3