Table 4.

Environmental exposure to metals and electromagnetic fields in transgenic mouse models of Alzheimer's disease.

Mouse model	Exposure	Duration of the exposure	Age at the start	Effect on brain	Effect on behavior	Reference
TgV337M	Aluminum-mltolate i.p. injection at various concentrations (50–100–200 μM)	Max 14 days	3 months	Al levels were too low to induce changes in tau phosphorylation in brain homogenates, but Al concentration was lethal	Not measured	[146]
Tg2576	Dietary aluminum (2 mg/kg diet)	9 months	3 months	↑ soluble and insoluble Aβ40 and Aβ42 in neocortical and hippocampal homogenates ↑ plaque load in hippocampus and neocortex ↑ oxidative stress markers	Not measured	[115]
Tg2576	Dietary aluminum lactate (1 mg/g diet)	120 days	5 months	No significant differences in Aβ40 and Aβ42 in cortical homogenates, no alterations in proliferation, survival or differentiation of BrdU-positive neurons in DG	No improvement MWM	[117]
Tg2576	Dietary aluminum lactate (1 mg/g diet)	6 months	5 months	↑ Al concentration in hippocampus and cerebellum ↑ Cu in hippocampus ↓ Fe in cerebellum ↑ Mn and Zn in neocortex, hippocampus and cerebellum	Not measured	[118]
Tg2576	Dietary aluminum lactate (1 mg/g diet)	6 months	5 months	↑ Al concentrations in the hippocampus, but no difference between WT and Tg animals, no difference in oxidative stress reaction in the hippocampus between WT and Tg	Not measured	[116]
APPswe/PS1ΔE9	Iron carbonyl (1 mg/ml)	3 days	P12	No difference in Aβ plaque load in hippocampus and temporal cortex, no difference in microglial activity ↑ GFAP levels in temporal cortex ↑ saturated fatty acids ↓ unsaturated fatty acids ↓ oxidative damage markers	Not measured	[130]
APPswe/PS1ΔE9	Zinc-deficient (<10 parts Zn per million (ppm))	3 months	9 months	No significant difference in serum zinc levels, no difference cortical volume ↑ 25% in total plaque volume, no difference in number of plaques or laminar distribution, no difference in oxidative stress markers	Not measured	[136]
Tg2576	Zinc in drinking water (10 ppm/0.153 mM Zn)	±12 months	From conception	↓ Aβ deposits in hilar and molecular region of the DG	↓ spatial memory in MWM both in Tg and WT, buth most pronounced in Tg	[137]
TgCRND8	Zinc in drinking water (10 ppm/0.153 mM Zn)	5 months	From weaning	No significant differences	↓ spatial memory in MWM both in Tg and WT, buth most pronounced in Tg	[137]
TgC100	Zinc in diet (ZnSO4, 1000, 500 or 300 ppm)	15 months	7 weeks	↑ Brain Zn levels in brain homogenates ↓ Cu levels (n.s.) ↓ Cu/Zn ratio ↓ 13% soluble Aβ 40 (trend) No changes in GFAP, SOD1, APP, C100, nor NF200 (neuron loss), no difference in intensity or distribution of Aβ or GFAP staining	Not measured	[138]
TgC100	Copper in diet (CuSO4 150 or 100 ppm)	7 weeks	9 months	No significant differences in Cu levels in brain homogenates ↑ Zn levels ↓ 18% soluble Aβ 40, no changes in GFAP, SOD1, APP, C100, nor NF200 (neuron loss), no difference in intensity or distribution of Aβ or GFAP staining	Not measured	[138]
3xTg	Copper sulfate (250 ppm) in 5% sucrose drinking water	3 or 9 months	2 months	3 months exposure: ↑ steady-state levels APP, C99 and BACE1 ↑ Aβ 40 in total plaque load in hippocampus, no alterations in total tau, phospho-tau nor Thy1.2 transcription activity ↑ AT8-positive neurons in CA1, no changes in steady-state levels of cdk5, p35/p25, GSK-3β or phospho-GSK-3β ↓ SOD1 activity in brain homogenates 9 months exposure: ↑ steady-state levels APP, C99, C83, BACE1, ADAM10 ↑ soluble Aβ40, phospho-tau, no alterations total tau levels ↑ p25 formation ↓ SOD1 activity	Not measured	[143]
AβPPsw	Electromagnetic field exposure (918 MHz, 0.25 W/kg ± 2 dB) 2 × 1 h p/d	7-8 month exposure	2 months 5 months	Young adult 7 months exposure, no significant differences in soluble Aβ in hippocampus + neocortex, no effect op hippocampal DNA repair enzymes, antioxidant enzyme markers, protein oxidative damage, nor striatal DNA oxidation Aged adult 8 months exposure ↓ Aβ plaque load in hippocampus (−35%) and entorhinal cortex (−32%) ↑ soluble Aβ in hippocampus + neocortex	Young adult 7 months exposure Prevention of cognitive deficits in retroactive interference ↑ Y-maze spontaneous alternation level No differences in open field activity, balance beam, string agility, and elevated plus maze Aged adult 8 months exposure Reversal of cognitive deficits	[27]