Alzheimer Disease:Mercury as pathogenetic factor

Joachim Mutter*,Johannes Naumann*,Catharina Sadaghiani*,Rainer Schneider*1Harald Walach*1

Correspondence to:

Joachim Mutter,MD
Institute for Environmental Medicine and Hospital Epidemiology
University Hospital Freiburg,
Hugstetter Str.55
79106 Freiburg,GER MA NY
PHONE:+49 761-270-5489
FA X:+49 761-270-5440
EMA I L :jmutter@iuk3.ukl.uni-freiburg.de

mercury;amalgam;Alzheimer's disease;neurotoxicity;
neurodegeneration;neurofibrillary tangles;Apolipoprotein E;
metals

The etiology of most cases of Alzheimer's disease (AD)is as yet unknown.
Epidemiological studies suggest that environmental factors may be involved beside genetic risk factors. Some studies have shown higher mercury concen-
trations in brains of deceased and in blood of living patients with Alzheimer's disease.Experimental tudies have found that even smallest amounts of mercury but no other metals in low concentrations were able to cause all nerve cell changes,which are typical for Alzheimer's disease.The most important genetic risk factor for sporadic Alzheimer's disease is the resence of the apolipoprotein Ee4 allele whereas the apolipoprotein Ee2 allele reduces the risk of devel-
oping Alzheimer's disease.Some investigators have suggested that apolipoprotein Ee4 has a reduced ability to bind metals like mercury and therefore explain the higher risk for Alzheimer's exisease. Therapeutic approaches embrace pharmaceuticals which bind metals in the brain of patients with Alzheimer's disease.
In sum,both the findings from epidemiological and demographical studies,the clinical tudies,experimental studies and the dental state of AD patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of AD.
R E V I E W A R T I C L E

Alzheimer's disease (AD)rarely occurs in early forms between the age of 30 and 65 (5 -10%),and frequently in late forms above the age of 65.On average the duration of the disease is 6 to 10 years,although
duration of survival decreases with increasing age.In
Alzheimer's disease causes costs abounding to an estimated 90 billion dollars [1 ].It ranks fourth
among all death causes,meanwhile infesting 4.5 mil-
According to estimations,a total of 16 million individuals will be affected by the year 2050 In recent years,the incidence of Alzheimer's disease has been on the rise.At least 30 -50%of all individuals above the age of 85 are affected in industrialized
With ever increasing life-spans Alzheimer's disease will be one of the major public health problems of coming decades.
generation and inflammatory processes,turbed and finally neuron death ensues in the entorhinal cortex,pus at early stages [5 -7 ].est in the nucleus basalis Meynert (Nbm)at advanced affection stages [8,9 ].of the cerebrum,ity status of the cortex,tex does not show much damage [5 -7 ].of Alzheimer's disease,Therefore,Accretion of A b mocysteine and metals [10 -14 ].neurotoxicity of amyloid accretions.

Synergistic effects of other metals
The Alzheimer's disease-typical neuronal changes
hyperphosphorylization of tau-protein,occurrence of neurofibrillary tangles,b -amyloid,tubulin inhi-bition,axon degeneration,increase of glutamine synthetase in the liquor)
found in nerve cells and animals may not be caused be other matals(lead cadmium, aluminum, copper, zinc, iron, chrome, but other metals may potentize mercury effects by contributing to oxidative stress.