Quecksilber und Alzheimer-Erkrankung

Higher mercury concentrations were found in brain regions and blood of some patients with Alzheimer's disease (AD). Low levels of inorganic mercury were able to cause AD- typical nerve cell deteriorations in vitro and in animal experiments. Other metals like zinc, aluminum, copper, cadmium, manganese, iron, and chrome are not able to elicit all of these deteriorations in low levels, yet they aggravate the toxic effects of mercury (Hg). Main human sources for mercury are fish consumption (Methyl-Hg) and dental amalgam (Hg vapour). Regular fish consumption reduces the risk of development of AD. Amalgam consists of approx. 50 % of elementary mercury which is constantly being vaporized and absorbed by the organism. Mercury levels in brain tissues are 2 - 10 fold higher in individuals with dental amalgam. Persons showing a genetically determined subgroup of transportation protein for fats (apolipoprotein E4) have an increased AD risk. Apoliprotein E (APO E) is found in high concentrations in the central nervous system. The increased AD risk through APO E4 might be caused by its reduced ability to bind heavy metals. Latest therapeutic approaches to the treatment of Alzheimer disease embrace pharmaceuticals which remove or bind metals from the brain. Preliminary success has been documented with chelation of synergistic toxic metals (Fe, Al, Zn, Cu) and therefore also Hg. The available data does not answer the question, whether mercury is a relevant risk factor in AD distinctively. In sum, the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of Alzheimer patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of Alzheimer's disease. Other factors currently discussed as causes (e. g. other metals, inflammations, dietetic factors, vitamin deficiency, oxidative distress, and metabolic impairments) may act as co-factors.

[1]  G. Severi,et al.  Dental Amalgam and Mercury Levels in Autopsy Tissues: Food for Thought , 2006, The American journal of forensic medicine and pathology.

[2]  J. Bartova,et al.  The beneficial effect of amalgam replacement on health in patients with autoimmunity. , 2004, Neuro endocrinology letters.

[3]  Graham N George,et al.  The Chemical Form of Mercury in Fish , 2003, Science.

[4]  P. Doraiswamy,et al.  Current Status of Metals as Therapeutic Targets in Alzheimer's Disease , 2003, Journal of the American Geriatrics Society.

[5]  D. Bennett,et al.  Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. , 2003, Archives of neurology.

[6]  Mark F Blaxill,et al.  Reduced Levels of Mercury in First Baby Haircuts of Autistic Children , 2003, International journal of toxicology.

[7]  A. Gritti,et al.  Inorganic mercury changes the fate of murine CNS stem cells , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  Robert L. Jones,et al.  Blood mercury levels in US children and women of childbearing age, 1999-2000. , 2003, JAMA.

[9]  J. Bartova,et al.  Dental amalgam as one of the risk factors in autoimmune diseases. , 2003, Neuro endocrinology letters.

[10]  C. Cattaneo,et al.  Should amalgam fillings be removed? , 2002, The Lancet.

[11]  A. Bush.  Metal complexing agents as therapies for Alzheimer’s disease , 2002, Neurobiology of Aging.

[12]  U. Lindh,et al.  Removal of dental amalgam and other metal alloys supported by antioxidant therapy alleviates symptoms and improves quality of life in patients with amalgam-associated ill health. , 2002, Neuro endocrinology letters.

[13]  M. Brockhaus,et al.  The effects of β-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and β-amyloid secretion , 2002, Neuroscience.

[14]  David Simon,et al.  ApoE genotype, past adult lead exposure, and neurobehavioral function. , 2002, Environmental health perspectives.

[15]  M. Berglund,et al.  Inorganic mercury and methylmercury in placentas of Swedish women. , 2002, Environmental health perspectives.

[16]  P. Zandi,et al.  Incidence of AD may decline in the early 90s for men, later for women , 2002, Neurology.

[17]  F. Giannerini,et al.  Influence of amalgam fillings on Hg levels and total antioxidant activity in plasma of healthy donors. , 2001, The Science of the total environment.

[18]  C. Masters,et al.  Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer's Disease Transgenic Mice , 2001, Neuron.

[19]  N. Syed,et al.  Retrograde degeneration of neurite membrane structural integrity of nerve growth cones following in vitro exposure to mercury , 2001, Neuroreport.

[20]  G Drasch,et al.  The Mt. Diwata study on the Philippines 1999--assessing mercury intoxication of the population by small scale gold mining. , 2001, The Science of the total environment.

[21]  M. Aschner,et al.  Mercuric chloride, but not methylmercury, inhibits glutamine synthetase activity in primary cultures of cortical astrocytes , 2001, Brain Research.

[22]  G. Roider,et al.  Content of non-mercury-associated selenium in human tissues , 2000, Biological Trace Element Research.

[23]  M. Aschner,et al.  Methylmercury alters glutamate transport in astrocytes , 2000, Neurochemistry International.

[24]  I. Roots,et al.  Molekulare Pathologie , 2000, Acta Chirurgica Austriaca.

[25]  R. Brookmeyer,et al.  Methods for projecting the incidence and prevalence of chronic diseases in aging populations: application to Alzheimer's disease. , 2000, Statistics in Medicine.

[26]  Y. Christen,et al.  Oxidative stress and Alzheimer disease. , 2000, The American journal of clinical nutrition.

[27]  M. Matsuoka,et al.  Mercury chloride activates c-Jun N-terminal kinase and induces c-jun expression in LLC-PK1 cells. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  C. Hock,et al.  Mercury Induces Cell Cytotoxicity and Oxidative Stress and Increases β‐Amyloid Secretion and Tau Phosphorylation in SHSY5Y Neuroblastoma Cells , 2000, Journal of neurochemistry.

[29]  H. Braak,et al.  Neuropathology of Alzheimer’s disease: what is new since A. Alzheimer? , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[30]  W. Brück,et al.  Glutamine synthetase in cerebrospinal fluid, serum, and brain: a diagnostic marker for Alzheimer disease? , 1999, Archives of neurology.

[31]  R. Corbo,et al.  Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? , 1999, Annals of human genetics.

[32]  W. D. Ehmann,et al.  Alzheimer's disease, dental amalgam and mercury. , 1999, Journal of the American Dental Association.

[33]  A. Hofman,et al.  Rates and risk factors for dementia and Alzheimer’s disease , 1999, Neurology.

[34]  R Clarke,et al.  Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. , 1998, Archives of neurology.

[35]  W. D. Ehmann,et al.  Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. , 1998, Neurotoxicology.

[36]  W. D. Ehmann,et al.  Trace elements in Alzheimer's disease pituitary glands , 1998, Biological Trace Element Research.

[37]  B. Haley,et al.  Abnormal properties of creatine kinase in Alzheimer's disease brain: correlation of reduced enzyme activity and active site photolabeling with aberrant cytosol-membrane partitioning. , 1998, Brain research. Molecular brain research.

[38]  T. Nyokong,et al.  The interaction of melatonin and its precursors with aluminium, cadmium, copper, iron, lead, and zinc: An adsorptive voltammetric study , 1998, Journal of pineal research.

[39]  A. Hofman,et al.  Dietary fat intake and the risk of incident dementia in the Rotterdam study , 1997, Annals of neurology.

[40]  J. Haines,et al.  Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis , 1997 .

[41]  W. D. Ehmann,et al.  Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress , 1996, Journal of the Neurological Sciences.

[42]  Steven T. DeKosky,et al.  Association between dementia and elevated TSH: A community-based study , 1996, Biological Psychiatry.

[43]  M. Boeniger,et al.  Neurodegenerative diseases: occupational occurrence and potential risk factors, 1982 through 1991. , 1996, American journal of public health.

[44]  P. Lichtenstein,et al.  Physical and mental health related to dental amalgam fillings in Swedish twins. , 1996, Community dentistry and oral epidemiology.

[45]  M. Beal,et al.  Oxidative damage in Alzheimer's , 1996, Nature.

[46]  B. Hyman,et al.  Apolipoprotein E and cognitive change in an elderly population , 1996, Annals of neurology.

[47]  C. Petito.  Neuropathological Diagnostic Criteria from Brain Banking , 1996 .

[48]  P. R. Yallapragada,et al.  Modulation of protein kinase C by heavy metals. , 1995, Toxicology letters.

[49]  D. Wekstein,et al.  Dental amalgam and cognitive function in older women: findings from the Nun Study. , 1995, Journal of the American Dental Association.

[50]  W. D. Ehmann,et al.  Elemental imbalances in the olfactory pathway in Alzheimer's disease , 1995, Journal of the Neurological Sciences.

[51]  A O Summers,et al.  Mercury exposure from “silver” tooth fillings: emerging evidence questions a traditional dental paradigm , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  KennethRockwood,et al.  The Canadian Study of Health and Aging* , 1994, Neurology.

[53]  H. Nakajima,et al.  Correlation of cytotoxicity with element release from mercury- and gallium-based dental alloys in vitro. , 1994, Dental materials : official publication of the Academy of Dental Materials.

[54]  J. Buckwalter,et al.  Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects. , 1994, Archives of neurology.

[55]  G. Roider,et al.  Mercury burden of human fetal and infant tissues , 1994, European Journal of Pediatrics.

[56]  V. Henderson,et al.  Estrogen deficiency and risk of Alzheimer's disease in women. , 1994, American journal of epidemiology.

[57]  D. McLachlan,et al.  Desferrioxamine and Alzheimer's Disease: Video Home Behavior Assessment of Clinical Course and Measures of Brain Aluminum , 1993, Therapeutic drug monitoring.

[58]  J. Weiner,et al.  The relationship between mercury concentration in human organs and different predictor variables. , 1993, The Science of the total environment.

[59]  T. Kruck.  Aluminium — Alzheimer's link? , 1993, Nature.

[60]  C. Bengtsson,et al.  Number of amalgam fillings in relation to cardiovascular disease, diabetes, cancer and early death in Swedish women. , 1993, Community dentistry and oral epidemiology.

[61]  Boyd E. Haley,et al.  Detection of glutamine synthetase in the cerebrospinal fluid of Alzheimer diseased patients: a potential diagnostic biochemical marker. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[62]  N. Brookes.  In vitro evidence for the role of glutamate in the CNS toxicity of mercury. , 1992, Toxicology.

[63]  H. Binder,et al.  [Epidemiologic progression of dementia diseases in Austria until the year 2050]. , 1992, Das Gesundheitswesen.

[64]  Peter Davies,et al.  Identification of normal and pathological aging in prospectively studied nondemented elderly humans , 1992, Neurobiology of Aging.

[65]  M Nylander,et al.  Mercury and selenium concentrations and their interrelations in organs from dental staff and the general population. , 1991, British journal of industrial medicine.

[66]  D. McLachlan,et al.  Intramuscular desferrioxamine in patients with Alzheimer's disease , 1991, The Lancet.

[67]  F. Lorscheider,et al.  Mercury exposure from "silver" fillings , 1991, The Lancet.

[68]  W. Markesbery,et al.  Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains , 1990, Brain Research.

[69]  L. Hahn,et al.  Whole‐body imaging of the distribution of mercury released from dental fillings into monkey tissues , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[70]  W. D. Ehmann,et al.  A search for longitudinal variations in trace element levels in nails of Alzheimer’s disease patients , 1990, Biological Trace Element Research.

[71]  J. Rungby,et al.  Traces of mercury in organs from primates with amalgam fillings. , 1990, Experimental and molecular pathology.

[72]  F. Lorscheider,et al.  Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings. , 1990, The American journal of physiology.

[73]  L. Hahn,et al.  Dental “silver” tooth fillings: a source of mercury exposure revealed by whole‐body image scan and tissue analysis , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[74]  W. Lukiw,et al.  New Evidence for an Active Role of Aluminum in Alzheimer's Disease , 1989, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[75]  C. Bengtsson,et al.  Number of amalgam tooth fillings in relation to subjectively experienced symptoms in a study of Swedish women. , 1988, Community dentistry and oral epidemiology.

[76]  M. Nylander,et al.  Correlation of dental amalgam with mercury in brain tissue. , 1987, The Journal of prosthetic dentistry.

[77]  M. Nylander.  MERCURY IN PITUITARY GLANDS OF DENTISTS , 1986, The Lancet.

[78]  F. Lorscheider,et al.  Serial Measurements of Intra-oral Air Mercury: Estimation of Daily Dose from Dental Amalgam , 1985, Journal of dental research.

[79]  J. Schubert,et al.  Combined effects in toxicology--a rapid systematic testing procedure: cadmium, mercury, and lead. , 1978, Journal of toxicology and environmental health.

[80]  Boyd E. Haley.  The relationship of the toxic effects of mercury to exacerbation of the medical condition classified as Alzheimer's disease , 2007 .

[81]  O. Pirk,et al.  [Treatment of Alzheimer's disease utilising the best available evidence-based medicine -- utopia?]. , 2005, Das Gesundheitswesen.

[82]  H. Walach,et al.  [Amalgam risk assessment with coverage of references up to 2005]. , 2005, Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)).

[83]  H. Kornhuber.  [Prevention of dementia (including Alzheimer's disease)]. , 2004, Das Gesundheitswesen.

[84]  D. Wojcik,et al.  Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity. , 2003, Journal of Alzheimer's disease : JAD.

[85]  The Children's Amalgam Trial: design and methods. , 2003, Controlled clinical trials.

[86]  R. Itzhaki,et al.  The significance of environmental factors in the etiology of Alzheimer's disease. , 2002, Journal of Alzheimer's disease : JAD.

[87]  G Drasch,et al.  Scientific comment on the German human biological monitoring values (HBM values) for mercury. , 2002, International journal of hygiene and environmental health.

[88]  H. Bickel.  [Dementia syndrome and Alzheimer disease: an assessment of morbidity and annual incidence in Germany]. , 2000, Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)).

[89]  V. Henderson,et al.  Oestrogens and dementia. , 2000, Novartis Foundation symposium.

[90]  Ivan Sterzl,et al.  Mercury and nickel allergy: risk factors in fatigue and autoimmunity. , 1999, Neuro endocrinology letters.

[91]  I. Bergdahl,et al.  Serum mercury concentration in relation to survival, symptoms, and diseases: results from the prospective population study of women in Gothenburg, Sweden. , 1999, Acta odontologica Scandinavica.

[92]  B. Dastugue,et al.  [Apolipoprotein E and Alzheimer's disease]. , 1998, Annales de biologie clinique.

[93]  J. Growdon,et al.  Increased blood mercury levels in patients with Alzheimer's disease , 1998, Journal of Neural Transmission.

[94]  R. Castellani,et al.  Reactive Oxygen Species Mediate Cellular Damage in Alzheimer Disease. , 1998, Journal of Alzheimer's disease : JAD.

[95]  Y. K. Fung,et al.  Brain mercury in neurodegenerative disorders. , 1997, Journal of toxicology. Clinical toxicology.

[96]  S. A. Winfield,et al.  Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain. , 1997, Neurotoxicology.

[97]  Boyd E. Haley,et al.  Inhibition of brain tubulin-guanosine 5'-triphosphate interactions by mercury: similarity to observations in Alzheimer's diseased brain. , 1997, Metal ions in biological systems.

[98]  W. Grant.  Dietary Links to Alzheimer's Disease , 1997 .

[99]  J. Claassen,et al.  Determination of blood mercury concentrations in Alzheimer's patients. , 1995, Journal of toxicology. Clinical toxicology.

[100]  K. Reuhl,et al.  The molecular basis of microtubule stability in neurons. , 1994, Neurotoxicology.

[101]  J. Slevin,et al.  HgEDTA complex inhibits GTP interactions with the E-site of brain beta-tubulin. , 1993, Toxicology and applied pharmacology.

[102]  H. Bickel,et al.  Epidemiologie der Demenz , 1992 .

[103]  K. Hall,et al.  Cross-cultural studies in Alzheimer's disease. , 1992, Ethnicity & disease.

[104]  E. Tiffany-Castiglioni,et al.  Reduction of glutamine synthetase activity in astroglia exposed in culture to low levels of inorganic lead. , 1991, Toxicology.

[105]  B. Winblad,et al.  Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer's disease. , 1991, Journal of neural transmission. Parkinson's disease and dementia section.

[106]  T. Powell,et al.  The Neuroanatomy of Alzheimer's Disease , 1989, Reviews in the neurosciences.

[107]  W. D. Ehmann,et al.  Trace element imbalances in hair and nails of Alzheimer's disease patients. , 1988, Neurotoxicology.

[108]  W. D. Ehmann,et al.  Regional brain trace-element studies in Alzheimer's disease. , 1988, Neurotoxicology.

[109]  B Lind,et al.  Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. , 1987, Swedish dental journal.

[110]  W. D. Ehmann,et al.  Brain trace elements in Alzheimer's disease. , 1986, Neurotoxicology.