Table 2.

Summary of the main clinical and preclinical findings supporting the involvement of zinc in AD.

Serum/CSF/brain zinc status—human data	References
↔ Serum zinc level in patients with and without cognitive impairment in the community	Haines et al., 1991
↔ Serum and hair zinc concentration in patients with AD	Shore et al., 1984
↑ Serum zinc level in AD epsilon 4 apoE allele carriers	Gonzalez et al., 1999
↑ Zinc serum in AD subjects compared with age-matched control subjects-postmortem study	Rulon et al., 2000
↓ Serum zinc level in AD patients	Baum et al., 2010
↓ Blood zinc in patients with AD than in controls	Brewer et al., 2010
↓ Serum zinc level in patients with senile dementia of the Alzheimer type (SDAT) when compared to control subjects	Jeandel et al., 1989
↓ Plasma zinc level in patients with AD compared with controls	Vural et al., 2010
↔ In CSF zinc level in patients with dementia of the Alzheimer type	Hershey et al., 1983; Sahu et al., 1988
↓ CSF zinc levels in AD patients as compared with controls	Molina et al., 1998
↓ Hippocampal zinc concentration in patients with AD—postmortem study	Corrigan et al., 1993
↓ Zinc level in both hemispheres of the superior frontal gyrus, the superior parietal gyrus, the medial temporal gyrus, the hippocampus and the thalamus in the AD patients—postmortem study	Panayi et al., 2002
↑ Zinc level in hippocampus and amygdala in AD patients—postmortem study	Danscher et al., 1997
↑ Tissue zinc in the AD-affected cortex compared with the control group	Religa et al., 2006
↑ Zinc in olfactory regions of AD patients as compared to control subjects	Samudralwar et al., 1995
↑ Zinc in amygdala and hippocampus in AD patients as compared to controls	Thompson et al., 1988
Zinc dyshomeostasis as a new therapeutic target in AD—animal study
Administration of DP-109 (the lipophilic metal chelator) reduced the aggregation of Aβ protein and deposition of amyloid plaques in aged female hAbetaPP-transgenic Tg2576 mice, compared to animals receiving vehicle treatment	Lee et al., 2004
Clioqunol (metal chelator) reduced zinc accumulation in the neuritic plaques and inhibit amyloidogenic AβPP processing in the AβPP/PS1 mouse brain	Wang et al., 2012
Carnosine supplementation in 3 × Tg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions	Corona et al., 2011
Selective intracellular release of zinc ions from bis(thiosemicarbazonato) complexes reduces levels of Alzheimer disease amyloid-beta peptide	Donnelly et al., 2008
Presenilins are important for cellular zinc turnover and has the potential to indirectly impact β-amyloid aggregation through metal ion clearance	Greenough et al., 2011
Zinc supplementation delays hippocampal-dependent memory deficits and reduces both Aβ and tau pathology in the hippocampus	Corona et al., 2010
Zinc dyshomeostasis as a new therapeutic target in AD—human study
PBT2 (copper/zinc ionophore) lowered CSF levels of Aβ and significantly improved cognition in AD patients	Lannfelt et al., 2008; Faux et al., 2010