3.1. A. Hallmark Brain Changes in Alzheimer’s Disease (AD)
- Senile Plaques: Neuritic plaques are composed of neuritic protein deposits found in excess amounts in AD brains. They are composed of beta amyloid protein .
- Amyloid Precursor Protein (APP): APP is the parent protein from which beta amyloid is derived. APP is broken down into fragments. A defect in APP may cause AD .
- Tau Protein: Accumulated phosphorylated tau protein is responsible for neurodegeneration in AD (13).
- Neurofibrillary Tangles (NFT): NFTs are a characteristic brain finding in AD, consisting of a hyperphosphorylated tau protein .Mercury: Mercury increases the phosphorylation of tau protein, resulting in NFTs .
- Memory Loss: Loss of memory is the hallmark symptom of AD .Mercury: Memory loss is a hallmark symptom of mercury toxicity .
3.2. B. Neurotransmitters
- Acetylcholine: Levels of acetylcholine are reduced in AD .Mercury: Acetylcholine is reduced in mercury toxicity .
- Serotonin: AD brains have a serotonin deficit .Mercury: Mercury inhibits the binding of serotonin to brain receptors .
- Dopamine: Dopamine levels in the AD brain are low, due to a deficiency of dopamine D2 receptors .Mercury: A negative correlation was found between total mercury and dopamine D2 receptors in the brain of wild mink .
- Glutamate: Excess glutamate leads to neurodegeneration in AD .Mercury: Mercury inhibits glutamate uptake and stimulates release of glutamate .
- Nitric Oxide: Excess nitric oxide can contribute to AD .Mercury: Mercury chloride induces nitric oxide synthetase .
- S-Adenosylmethione (SAMe): AD patients with depression have decreased levels of SAMe .Mercury: Mercury inhibits SAMe .
- Norepinephrine: AD brains have decreased levels of norepinephrine .Mercury: Mercury decreases norepinephrine in brain synapses .
3.3. C. Enzymes
- BACE 1 (Beta Amyloid Cleaving Enzyme): BACE 1 has been implicated as the enzyme responsible for plaque in AD brains .
- Gamma Secretase: Early-onset AD patients have mutations in genes that produce gamma secretase, which increases beta amyloid protein .Mercury: Mercury inhibits gamma secretase, suggesting the inhibition contributes to mercury-induced neuron toxicity .
- Kinases: Kinases are protein enzymes responsible for phosphorylation of hydroxyl proteins. The enzyme has a high concentration in AD .Mercury: Mercury induces hyperphosphorylation by activating kinase pathways .
- Cyclooxygenase-2 (Cox-2): Cox-2 is released during inflammation and is over-expressed in AD .Mercury: Mercury induces expression of cox-2 .
- Cytochrome-c-oxidase: Deficiencies of cytochrome-c-oxidase have been reported in AD patients .Mercury: Mercuric chloride inhibits cytochrome-c-oxidase .
- Monaamine Oxidase (MAO): MAO forms hydrogen peroxide which is higher in AD .Mercury: Mercury increases MAO activity .
- Nitric Oxide Synthetase: Elevated levels of nitric oxide synthetase contribute to AD .Mercury: Mercury induces nitric oxide synthetase .
- Acetyl Choline Transferase (CAT): CAT is reduced by up to 90 percent in AD .Mercury: Mercury inhibits CAT .
- Caspases: In AD, there is activation of apoptosis caspases that underlie the pathology of AD .Mercury: Mercury increases activated caspases .
3.4. D. Immunity
- Complement: AD is triggered by the activation of complement 1 .Mercury: Studies show a correlation between mercury vapor and complement .
- Cytokines: Cytokines contribute to inflammation. The beta amyloid in AD inflames the surrounding microglial cells .Mercury: Mercury significantly induces cytokine expression .
- Glial Fibrillary Acid Protein Antibodies (GFAP): GFAP are autoantibodies associated with AD .Mercury: Methyl mercury induces GFAP .
- Interleukin 1 (IL-1): Over-expression of IL-1 in AD sets the cytokine cycle in motion .Mercury: Mercuric chloride increases the release of IL-1 .
- Transforming Growth Factor Beta 1 (TGF B-1): TGF B-1 regulates beta amyloid precursor protein synthesis. It is a cytokine that plays a central role in AD .Mercury: Thimerosal contains ethyl mercury, which enhances the expression of TGF B-1 .
- Tumor Necrosis Factor (TNF): Is a cytokine that contributes to AD. Excess levels of TNF are found in the cerebral fluid of AD .Mercury: Low levels of mercuric chloride increase the release of TNF .
- Beta-2 Microglobulin (B-2 M): B-2 Microglobulin is a peptide that is increased in the amyloid disorder of AD .Mercury: B-2 Microglobulins are used as an early indicator of mercury toxicity in the kidney .
- Inflammation: AD brains show evidence of inflammation adjacent to plaques .Mercury: Mercury exposure increases pro-inflammatory cytokines .
- Phosphodiesterase 4 (PDE 4): PDE 4 is an enzyme that degrades cyclic amp (CAMP). CAMP underlies memory formation .Mercury: Mercury has been found to stimulate PDE 4 and reduce CAMP .
3.5. E. Genetic
- Apolipoprotein E4 (APOE4): APOE4 may account for 60% of all AD cases. APOE 4 appears to promote the binding of the amyloid beta protein, facilitating the formation of plaque .Mercury: APOE4 has a reduced ability to bind mercury, and thus potentiates mercury damage .
- Genetic Mutations: Nearly 30% of early-onset AD is linked to the presenilin 1 gene .Mercury: Mercury is known to cause gene mutations .
- Presenilin Gene Mutation: In the Antioguia region of Columbia, families with the Paisa presenilin 1 gene mutation develop AD nearly ten years earlier than individuals with the exact same mutation in Japan .Mercury: In the Antioguia region, individuals are exposed to the highest levels of mercury in the world from gold mines .
- Alpha-2 Macroglobulins (A2M): A2M is a gene suspected of controlling the rate of beta amyloid protein production and is a possible susceptible gene for AD .Mercury: A2M levels were found to be significantly higher in mercury exposed workers .
- Hippocampus DNA Synthesis: AD is characterized by the death of cells in the hippocampus .Mercury: Mercury inhibits DNA synthesis by 44 percent in the hippocampus of rats .
3.6. F. Minerals
- Aluminum: Studies suggest an association between AD and aluminum .Mercury: Aluminum dramatically enhances mercury toxicity .
- Calcium: Amyloid beta protein is increased in AD, which disturbs calcium concentrations and the calcium metabolism .Mercury: Mercury increases intracellular calcium concentrations .
- Copper: The Nun Study on AD found an association between high serum copper and AD .Mercury: Mercury can tie up metallothionein so the body cannot clear out toxic metals such as copper .
- Iron: Increased levels of the iron-binding protein melanotransferrin is seen in AD. Iron deposits are found in senile plaques. Beta amyloid production is increased in the presence of iron .Mercury: Iron levels in the blood have been correlated with mercury and memory .
- Magnesium: Magnesium levels are depleted within the hippocampus of AD .Mercury: Mercury competes with magnesium and interferes with magnesium-dependent pathways .
- Zinc: Zinc tends to accumulate in the areas of the brain most prone to AD damage. Zinc is suspected of aggregating beta amyloid deposits and pulls copper into the deposits. Zinc levels in the hippocampus are decreased in AD .Mercury: Mercury tends to displace zinc in energy producing pathways for neurotransmitters because they have a similar chemical structure .
- Selenium: Studies have shown that AD patients have lower levels of selenium in their plasma .Mercury: Selenium binds to mercury and neutralizes toxicity. Workers in mercury mines have lower levels of selenium in their blood .
3.7. H. Vitamins
- Folic Acid/Folate: Low levels of folic acid increase the risk of AD .Mercury: Studies have found a negative correlation between serum folate and blood mercury ;
- Thiamine (Vitamin B1): Low levels of vitamin B1 increase the risk of developing AD .Mercury: Mercury reduces brain levels of vitamin B1 .
- Vitamin B12: AD is characterized by vitamin B12 deficiencies .Mercury: Mercury can reduce the uptake of vitamin B12 .
- Vitamin C: Evidence suggests that vitamin C may prevent the onset of AD .Mercury: Workers exposed to mercury had lower levels of plasma ascorbic acid .
- Vitamin E: Vitamin E deficiencies have been associated with AD .Mercury: Vitamin E provides complete protection from mercury toxicity in poisoned rats .
- Vitamin D: Vitamin D may play a role in the pathophysiology of cognition decline in AD .Mercury: Little research has been done with mercury and vitamin D. Vitamin D deficiencies in AD may be explained by a lack of sun exposure. Vitamin D is anti-inflammatory, and mercury is known to cause inflammation.
3.8. I Amino Acids, Antioxidants, and Biochemicals
- Homocysteine: Homocysteine is elevated in AD and is toxic to the brain. It is associated with brain shrinkage .Mercury: Mercury toxicity overwhelms SAMe, resulting in elevated homocysteine .
- Arachidonic Acid: Arachidonic acid induces the polymerization of tau and induces apoptosis in neurons .Mercury: Methyl mercury induces the production of arachidonic acid in cerebellar granule cells .
- DHEA Sulfate: The ratio of DHEA sulfate to cortisol is significantly lower in AD .Mercury: Mercury contributes to lower levels of DHEA .
- Glutathione: Glutathione is essential for removing free radicals from the brain .Mercury: Rat studies have shown that mercury inhibits glutathione. In mercury toxicity, levels of glutathione decline and brain damage occurs .
- Antioxidants: Free radicals are responsible for oxidative cell death associated with the amyloid beta protein in AD .Mercury: Mercury produces free oxygen radicals that cause nerve damage .
- Hydrogen Peroxide: Beta amyloid protein in AD increases the production of hydrogen peroxide .Mercury: The uptake of mercury vapor into cells is increased by hydrogen peroxide .
- Lipid Peroxidation: The accumulation of lipid peroxidation products has been found in AD brains .Mercury: Mercury promotes lipid peroxidation .
- Glycosaminoglycans (GAGs): GAGs are found in AD brain plaques. Sulfated GAGs have an affinity for beta amyloid .Mercury: Rat studies have shown that mercuric chloride increases serum GAGs .
- Brain Derived Neurotrophic Factor (BDNF): BDNF is a cytokine that influences nerve growth in brains .Mercury: Rat studies have shown methyl mercury-induced cell death occurs by way of receptors of BDNF .
- Melatonin: Melatonin levels, which regulate sleep and wakefulness, are low in AD .Mercury: Melatonin protects against mercury toxicity .
- High Density Lipoprotein (HDL): HDL, the good cholesterol, reduces the risk of developing AD .Mercury: Low HDL cholesterol is associated with high blood mercury .
3.9. J. Other Factors
- Platelets: In AD, platelet activation rates are 30% to 50% higher compared to non-AD subjects .Mercury: Normal platelet function is affected by high and low concentrations of mercury. Low mercury levels encourage clotting of red blood cells .
- Odor Identification: Subjects who have a mild cognition impairment and poor odor identification scores are more likely to develop AD .Mercury: Loss of smell is a symptom of mercury toxicity .
- Smoking: Smoking increases the risk of AD .Mercury: Dopamine levels are reduced in AD. Smoking increases neurotransmitters, such as dopamine, that can be seen as self-medicating . One study found that subjects with mercury dental amalgams smoked significantly more than a control group without amalgams who were age and sex matched. Animal studies have shown a negative correlation between total mercury and dopamine D2 receptors (24).
- Herpes Virus: A high percentage of AD brains contain latent herpes simplex virus .Mercury: Mercury exposure increases herpes virus replication .
- Chlamydia Pneumonia: Chlamydia bacterium has been found in parts of the brain of late-onset AD .Mercury: Mercury has been found to increase chlamydia infections in animals .
- African Americans: AD is very rare in west Africa. In the U.S., African Americans have an AD rate two times higher than whites .Mercury: In lakes across tropical Africa, fish have low levels of mercury .
- Depression: Depression is more likely to occur in mild to moderate AD .Mercury: A major symptom of mercury toxicity is depression . Studies have found that subjects with mercury dental amalgams suffered significantly more from depression than subjects without amalgams who were age and sex matched.
- Hypertension: Chronic hypertension increases the risk of AD .Mercury: Serum mercury concentrations are associated with hypertension .
- Parkinson’s Disease (PD): Up to one third of PD patients develop AD .Mercury: Many epidemiological studies have shown an association between PD and exposure to mercury ;
- Down Syndrome: All patients with Down Syndrome will develop neuropathological hallmarks of AD ;Mercury: An Egyptian study found elevated serum mercury levels in the Down Syndrome group compared to a control group, and they had a significant increase in DNA damage .
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|A. Hallmark Changes|
|1. Senile Plaques—both increased;|
|2. Amyloid Precursor Protein—both decreased;|
|3. Tau Protein—both increased;|
|4. Neurofibrillary Tangles—both increased;|
|5. Memory—both decreased.|
|1. Acetylcholine—both decreased;|
|2. Serotonin—both decreased;|
|3. Dopamine—both decreased;|
|4. Glutamate—both increased;|
|5. Nitric Oxide—both increased;|
|6. S Adenosylmethione (SAMe)—both decreased;|
|7. Norepinephrine—both decreased.|
|1. BACE 1 (Beta Amyloid Clearing Enzyme)—both increased;|
|2. Gamma Secretase—both decreased;|
|3. Caseine Kinase (CK-P)—both decreased;|
|4. Cyclooxygenase-2 (Cox-2)—both increased;|
|5. Cytochrome C Oxidase—both decreased;|
|6. Kinases—both increased;|
|7. Monaamine Oxidase (MAO)—both increased;|
|8. Nitric Oxide Synthetase (NOS)—both increased;|
|9. Capases—both increased.|
|1. Complement—both increased;|
|2. Cytokines—both increased;|
|3. Glial Fibrillary Acid Protein Antibodies (GFAP)—both increased;|
|4. Interleukin 1 (IL-1)—both increased;|
|5. Transforming Growth Factor Beta (TGF B1)—both increased;|
|6. Tumor Necrosis Factor (TNF)—both increased;|
|7. Beta-2 Microglobulin—both increased;|
|8. Inflammation—both increased;|
|9. Phosphodiesterase 4 (PPE-4)—both decreased.|
|1. Apolipoptotein E4—both related;|
|2. Genetic Mutations—both related;|
|3. Alpha 2 Macroglobulin (A2M)—both increased;|
|4. Hippocampus DNA Synthesis—both related.|
|1. Aluminum—both related;|
|2. Calcium—both increased;|
|3. Copper—both related;|
|4. Iron—both related;|
|5. Magnesium—both decreased;|
|6. Zinc—both related;|
|7. Selenium—both decreased.|
|1. Folic acid/folate—both decreased;|
|2. Thiamine—both decreased;|
|3. Vitamin B12—both decreased;|
|4. Vitamin C—both decreased;|
|5. Vitamin E—both decreased;|
|6. Vitamin D—both related.|
|H. Amino Acids, Antioxidants, and Biochemical Changes|
|1. Homocysteine—both increased;|
|2. Arachidonic Acid—both increased;|
|3. DHEA Sulfate—both decreased;|
|4. Glutathione—both decreased;|
|5. Antioxidants—both related;|
|6. Hydrogen Peroxide—both decreased;|
|7. Lipid Peroxidation—both increased;|
|8. Glycoaminoglycans—both increased;|
|9. Acetyl-L Carnitine—both related;|
|10. Brain Derived Neurotrohic Factor (BDNF)—both related;|
|11. Melatonin—both decreased;|
|12. High Density Lipoprotein—both decreased.|
|I. Other Factors|
|1. Platelets—both increased;|
|2. Odor Identification—both decreased;|
|3. Smoking—both increased;|
|4. Herpes Virus—both increased;|
|5. Chlamydia Pneumonia—both increased;|
|6. African Americans—both related;|
|7. Depression—both increased;|
|8. Hypertension—both increased;|
|9. Parkinsons Disease—both increased;|
|10. Downs Syndrome—both increased.|
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