Water quality has a pronounced effect on cholesterol-induced accumulation of Alzheimer amyloid β (Aβ) in rabbit brain

Increased circulating cholesterol is known to promote risk of coronary artery disease. It is now emerging that cholesterol promotes production and accumulation of amyloid β (Aβ) deposited in the hallmark pathologic lesion of Alzheimer's disease (AD), the senile plaque, perhaps by shifting away from normal metabolism of amyloid β protein precursor (AβPP) to Aβ. Previous studies employing the cholesterol-fed rabbit model of AD demonstrated that induction of AD-like Aβ accumulation in brain could be reversed by co-administration of cholesterol lowering drugs or removing cholesterol, prompted initiation of an AD Cholesterol-Lowering (Statin) Treatment Trial. We now present data that identify a previously unrecognized role for dietary water quality on the severity of neuropathology induced by elevated cholesterol. Neuronal accumulation of Aβ induced by increased circulating concentrations of cholesterol in the New Zealand white rabbit is attenuated when distilled drinking water is administered compared to use of tap water. The numbers of neurons in cholesterol-fed rabbits that exhibited Aβ immunoreactivity, relative to normal chow-fed controls, increased ∼ 2.5 fold among animals on tap water but only ∼ 1.9 fold among animals on distilled water. This yielded a statistically significant ∼ 28% reduction due to the use of distilled water. In addition, the subjectively assessed intensity of neuronal Aβ immunoreactivity was consistently reduced among cholesterol-fed rabbits allowed distilled drinking water compared to cholesterol-fed rabbits on tap water. As intensity of antibody immunoreactivity is likely related to concentration of antigen, the identified difference among cholesterol-fed rabbits allowed distilled drinking water may hold greater importance than a significant reduction in numbers of affected neurons. The effect on neuronal Aβ immunoreactivity intensity was observable among cholesterol-fed rabbits reared and allowed tap water when performing studies in three distinct locales. Pilot data suggest the possibility of increased clearance of Aβ from the brain, identified as increased blood levels, among cholesterol-fed rabbits administered distilled water compared to animals on tap water. The agent(s) occurring in tap water, excluded by distillation, promoting accumulation of neuronal Aβ immunoreactivity is(are) yet undisclosed, but arsenic, manganese, aluminum, zinc, mercury, iron and nitrate have tentatively been excluded because they were not identifiable (below detection limits) in the tap water of the three locales where the cholesterol-induced neuropathologic difference was observable. These findings suggest that water quality may impact on human health in the setting of increased circulating cholesterol levels, and could illustrate a truly simple life-style change that could be of benefit in AD.