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MEDLINE

 

Water quality has a pronounced effect on

cholesterol-induced accumulation of Alzheimer amyloid

beta (Abeta) in rabbit brain.

J Alzheimers Dis 2002 Dec;4(6):523-9 (ISSN:

1387-2877)

Sparks DL; Lochhead J; Horstman D; Wagoner T; Martin T

 

Sun Health Research Institute, Sun City, Arizona

85351, USA.

Increased circulating cholesterol is known to promote

risk of coronary artery disease. It is now emerging

that cholesterol promotes production and accumulation

of amyloid beta (Abeta) deposited in the hallmark

pathologic lesion of Alzheimer's disease (AD), the

senile plaque, perhaps by shifting away from normal

metabolism of amyloid beta protein precursor (AbetaPP)

to beta. Previous studies employing the

cholesterol-fed rabbit model of AD demonstrated that

induction of AD-like Abeta 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 Abeta 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 Abeta

immunoreactivity, relative to normal chow-fed

controls, increased approximately 2.5 fold among

animals on tap water but only approximately 1.9 fold

among animals on distilled water. This yielded a

statistically significant approximately 28% reduction

due to the use of distilled water.

 

In addition, the subjectively assessed intensity of

neuronal Abeta 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 Abeta 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 Abeta 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 Abeta 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.

Major Subject Heading(s) Minor Subject Heading(s) CAS

Registry / EC Numbers

Alzheimer Disease [pathology]

Amyloid beta-Protein [metabolism]

Brain [pathology]

Cholesterol [blood]

Water Pollution, Chemical [adverse effects]

Water Purification

Animals

Hypercholesterolemia [pathology]

Rabbits

Risk Factors

0 (Amyloid beta-Protein)

57-88-5 (Cholesterol)

 

 

Indexing Check Tags: Human; Male; Support, Non-U.S.

Gov't

Language: English

MEDLINE Indexing 200307

Publication Type: Owner: NLM

Publication Type: Journal Article

PreMedline Identifier: 0012515903

Journal Code: IM