silicon and Alzheimer-Disease

The prevalence of degenerative diseases has risen in western countries. Growing evidence suggests that demenia and other cognition affectations are associated with ambient factors including specific nutrients, food ingredients or specific dietary patterns. Mediterranean diet adherence has been associated with various health benefits and decreased risk of many diseases, including neurodegenerative disorders. Beer, as part of this protective diet, contains compounds such as silicon and hops that could play a major role in preventing brain disorders. In this review, different topics regarding Mediterranean diet, beer and the consumption of their main compounds and their relation to neurological health have been addressed. Taking into account published results from our group and other studies, the hypothesis linking aluminum intoxication with dementia and/or Alzheimer's disease and the potential role of regular beer has also been considered. Beer, in spite of its alcohol content, may have some health benefits; nonetheless, its consumption is not adequate for all subjects. Thus, this review analyzed some promising results of non-alcoholic beer on several mechanisms engaged in neurodegeneration such as inflammation, oxidation, and cholinesterase activity, and their contribution to the behavioral modifications induced by aluminum intoxication. The review ends by giving conclusions and suggesting future topics of research related to moderate beer consumption and/or the consumption of its major compounds as a potential instrument for protecting against neurodegenerative disease progression and the need to develop nutrigenetic and nutrigenomic studies in aged people and animal models.

Topics: Aluminum; Alzheimer Disease; Beer; Diet, Mediterranean; Humans; Neuroprotection; Nutritive Value; Silicon

Silicon is the second most abundant element in nature behind oxygen. As a metalloid, silicon has been used in many industrial applications including use as an additive in the food and beverage industry. As a result, humans come into contact with silicon through both environmental exposures but also as a dietary component. Moreover, many forms of silicon, that is, Si bound to oxygen, are water-soluble, absorbable, and potentially bioavailable to humans presumably with biological activity. However, the specific biochemical or physiological functions of silicon, if any, are largely unknown although generally thought to exist. As a result, there is growing interest in the potential therapeutic effects of water-soluble silica on human health. For example, silicon has been suggested to exhibit roles in the structural integrity of nails, hair, and skin, overall collagen synthesis, bone mineralization, and bone health and reduced metal accumulation in Alzheimer's disease, immune system health, and reduction of the risk for atherosclerosis. Although emerging research is promising, much additional, corroborative research is needed particularly regarding speciation of health-promoting forms of silicon and its relative bioavailability. Orthosilicic acid is the major form of bioavailable silicon whereas thin fibrous crystalline asbestos is a health hazard promoting asbestosis and significant impairment of lung function and increased cancer risk. It has been proposed that relatively insoluble forms of silica can also release small but meaningful quantities of silicon into biological compartments. For example, colloidal silicic acid, silica gel, and zeolites, although relatively insoluble in water, can increase concentrations of water-soluble silica and are thought to rely on specific structural physicochemical characteristics. Collectively, the food supply contributes enough silicon in the forms aforementioned that could be absorbed and significantly improve overall human health despite the negative perception of silica as a health hazard. This review discusses the possible biological potential of the metalloid silicon as bioavailable orthosilicic acid and the potential beneficial effects on human health.

Topics: Alzheimer Disease; Animals; Atherosclerosis; Humans; Silicon; Silicon Dioxide

Silicon is an essential element for some lower forms of life. However, it is not generally considered an essential nutrient for mammals and the mechanisms underlying its potential essentiality remain partially unknown. In recent years, a possible association between the aluminum and silicon levels in drinking water and Alzheimer's disease (AD) has been suggested. It has been reported that silicon might have a protective effect for limiting oral aluminum absorption. This review is focused primarily on the potential role of silicon in preventing oral aluminum absorption and retention in mammals. The results of a number of studies suggest that dietary silicon supplementation could be of therapeutic value for preventing chronic aluminum accumulation in the brain, and hence, be a potential therapy for AD. However, it must be noted that controversy remains about whether aluminum accumulation in the brain is a cause or a consequence of AD. It is suggested that further investigation of this issue is warranted.

Topics: Administration, Oral; Aluminum; Alzheimer Disease; Brain; Dietary Supplements; Humans; Intestinal Absorption; Silicon

Topics: Aluminum; Aluminum Silicates; Alzheimer Disease; Brain; Down Syndrome; Humans; Renal Dialysis; Silicon

Topics: Acetylcholine; Acetylcholinesterase; Age Factors; Aged; Aluminum; Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Brain; Brain Chemistry; Cell Count; Cognition; Craniocerebral Trauma; Delirium; Dementia; Diagnosis, Differential; Female; Humans; Interpersonal Relations; Male; Memory; Middle Aged; Neurofibrils; Neurotransmitter Agents; Personality; Sex Factors; Silicon; Thyroid Diseases; Tomography, Emission-Computed

There has been a plausible link between human exposure to aluminum and Alzheimer's disease for several decades. We contend that the only direct and ethically acceptable experimental test of the 'aluminum hypothesis', which would provide unequivocal data specific to the link, is to test the null hypothesis that a reduction in the body burden of aluminum to its lowest practical limit would have no influence upon the incidence, progression, or severity of Alzheimer's disease. Herein we are testing the hypothesis that silicon-rich mineral waters can be used as non-invasive methods to reduce the body burden of aluminum in individuals with Alzheimer's disease and a control group consisting of their carers and partners. We have shown that drinking up to 1 L of a silicon-rich mineral water each day for 12 weeks facilitated the removal of aluminum via the urine in both patient and control groups without any concomitant affect upon the urinary excretion of the essential metals, iron and copper. We have provided preliminary evidence that over 12 weeks of silicon-rich mineral water therapy the body burden of aluminum fell in individuals with Alzheimer's disease and, concomitantly, cognitive performance showed clinically relevant improvements in at least 3 out of 15 individuals. This is a first step in a much needed rigorous test of the 'aluminum hypothesis of Alzheimer's disease' and a longer term study involving many more individuals is now warranted.

Topics: Aged; Aluminum; Alzheimer Disease; Cognition; Copper; Female; Humans; Incidence; Iron; Male; Middle Aged; Mineral Waters; Risk Factors; Silicic Acid; Silicon; Treatment Outcome; Water Supply

Topics: Aluminum; Alzheimer Disease; Case-Control Studies; England; Humans; Silicon; Water Supply

Alzheimer's disease (AD) is a major group of diseases that threaten human health, and the search for drugs and treatments for it has never stopped. Research and development of NMDA receptor antagonists as potential therapeutic targets have also been ongoing. Our group designed and synthesized 22 new tetrahydropyrrolo[2,1-b]quinazolines based on NR2B-NMDARs targets and evaluated them for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, A21 exhibited excellent neuroprotective activity. Subsequently, the structure-activity relationships and inhibitor binding modes of the tetrahydropyrrolo[2,1-b]quinazolines were further analyzed by molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The results showed that A21 could match the two binding pockets of NR2B-NMDARs. The research results of this project will lay a certain foundation for the research of novel NR2B-NMDA receptor antagonists and also provide new ideas for the subsequent research and development of this target.

Topics: Alzheimer Disease; Humans; Molecular Docking Simulation; Quinazolines; Receptors, N-Methyl-D-Aspartate; Silicon; Structure-Activity Relationship

The redox-active metal ions, especially Cu

Topics: Alzheimer Disease; Amyloid beta-Peptides; Carbon; Chelating Agents; Copper; Humans; Metals; Oxidative Stress; Silanes; Silicon; Silicon Dioxide

We show that commercially sourced n-channel silicon field-effect transistors (nFETs) operating above their threshold voltage with closed loop feedback to maintain a constant channel current allow a pH readout resolution of (7.2 ± 0.3) × 10

Topics: Alzheimer Disease; Cyclin-Dependent Kinase 5; Electrochemical Techniques; Humans; Hydrogen-Ion Concentration; Neuroprotective Agents; Peptides; Silicon; Transistors, Electronic

Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO

Topics: Alzheimer Disease; Animals; Brain; Cell Survival; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Nanostructures; Nerve Growth Factor; PC12 Cells; Porosity; Rats; Silicon; X-Ray Microtomography

Multitargeting or polypharmacological approaches, looking for single chemical entities retaining the ability to bind two or more molecular targets, are a potentially powerful strategy to fight complex, multifactorial pathologies. Unfortunately, the search for multiligand agents is challenging because only a small subset of molecules contained in molecular databases are bioactive and even fewer are active on a preselected set of multiple targets. However, collections of natural compounds feature a significantly higher fraction of bioactive molecules than synthetic ones. In this view, we searched our library of 1175 natural compounds from marine sources for molecules including a 2-aminoimidazole+aromatic group motif, found in known compounds active on single relevant targets for Alzheimer's disease (AD). This identified two molecules, a pseudozoanthoxanthin (1) and a bromo-pyrrole alkaloid (2), which were predicted by a computational approach to possess interesting multitarget profiles on AD target proteins. Biochemical assays experimentally confirmed their biological activities. The two compounds inhibit acetylcholinesterase, butyrylcholinesterase, and β-secretase enzymes in high- to sub-micromolar range. They are also able to prevent and revert β-amyloid (Aβ) aggregation of both Aβ

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Butyrylcholinesterase; Cholinesterase Inhibitors; Humans; Ligands; Peptide Fragments; Silicon

We present a surface assisted laser desorption ionization (SALDI) technique, coupled with fluorocarbon coating, to achieve selective segregation of ionic and/or hydrophilic analytes from background biofluid electrolytes for quantiatve mass spectrometric analysis. By controlling the contact angle of (1H,1H,2H,2H-perfluorooctyl) trichlorosilane or (1H,1H,2H,2H-perfluorooctyl) dimethylchlorosilane to a specific range (105-120°), background electrolytes can be made to segregate from hydrophilic analytes during a drying step on the surface of a highly nanoporous thin film. Nanoporous silicon films were prepared using glancing angle deposition (GLAD) thin film technology, then coated with fluorcarbon. This desalting method directly separates highly polar, ionic metabolites, such as amino acids, from salty biofluids such as aritificial cerebrospinal fluid (aCSF) and serum. Derivatization, extraction and rinsing steps are not required to separate the analytes from the bioelectrolytes. With on-chip desalting, the limit of quantitation for histidine spiked in aCSF is ∼1 μM, and calibration curves with internal standards can achieve a precision of 1-9% within a 1 to 50 μM range. Five highly polar organic acids in serum were successfully quantified, and the SALDI-MS results obtained on the desalted serum sample spots show both good reproducibility and compare well to results from NMR and liquid chromatography-mass spectrometry. Putative identification of a total of 32 metabolites was accomplished in blood using time-of-flight MS with perfluoro coated Si-GLAD SALDI, by comparison to tabulated data.

Topics: Alzheimer Disease; Amino Acids; Cerebrospinal Fluid; Electrolytes; Fluorocarbons; Humans; Hydrophobic and Hydrophilic Interactions; Nanostructures; Particle Size; Porosity; Salts; Silicon; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface Properties

The aim of this work is to develop a sensitive and specific immune-sensing platform dedicated to the detection of potential biomarkers of Alzheimer's disease (AD) in biological fluids. Accordingly, a controlled and adaptive surface functionalization of a silicon wafer with 7-octenyltrichlorosilane has been performed. The surface has extensively been characterized by atomic force microscopy (AFM; morphology) and X-ray photoelectron spectroscopy (XPS; chemical composition) and contact angle measurements. The wettability of the grafted chemical groups demonstrated the gradual trend from hydrophilic to hydrophobic surface during functionalization. XPS evidenced the presence of silanes on the surface after silanization, and even carboxylic groups as products from the oxidation step of the functionalization process. The characterization results permitted us to define an optimal protocol to reach a high-quality grafting yield. The issue of the quality of controlled chemical preparation on bioreceiving surfaces was also investigated by the recognition of one AD biomarker, the amyloid peptide Aβ 1-42. We have therefore evaluated the biological activity of the grafted anti Aβ antibodies onto this silanized surface by fluorescent microscopy. In conclusion, we have shown, both qualitatively and quantitatively, the uniformity of the optimized functionalization on slightly oxidized silicon surfaces, providing a reliable and chemically stable procedure to determine specific biomarkers of Alzheimer disease. This work opens the route to the integration of controlled immune-sensing applications on lab-on-chip systems.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Biosensing Techniques; Humans; Immunoglobulin G; Lab-On-A-Chip Devices; Peptide Fragments; Silanes; Silicon; Surface Properties

In this work, we present a highly sensitive immunoassay for the detection of the Alzheimer's disease (AD) biomarker amyloid-beta 1-42 (Aβ42) based on a label/label-free microarray platform that utilises silicon/silicon oxide (Si/SiO2) substrates. Due to constructive interference, Si/SiO2 layered slides allow enhancement of the fluorescence intensity on the surface with significant improvements in sensitivity of detection. The same substrate allows the label-free multiplexed detection of targets using the Interferometric Reflectance Imaging Sensor (IRIS), a platform amenable to high-throughput detection of mass changes on microarray substrates. Silicon chips are coated with copoly(DMA-NAS-MAPS), a ter-copolymer made from dimethylacrylamide (DMA), 3-(trimethoxysilyl)propyl methacrylate (MAPS) and N-Acryloyloxy succinimide (NAS). Aβ42 aggregation was studied by circular dichroism (CD), and an optimal antibody pair was selected based on specificity of recognition, binding yield and spot morphology of the capture antibody on the coated silicon surface as analysed by IRIS. Finally, incubation conditions were optimised, and an unprecedented Aβ42 detection sensitivity of 73pg/mL was achieved using an artificial cerebrospinal fluid (CSF) sample. Because of their multiplexing capability, low volume sample consumption and efficient sample-to-result time for population-wide screening, microarrays are ideal tools for the identification of individuals with preclinical AD who are still cognitively healthy. The high sensitivity of this assay format, potentially coupled to a pre-concentration step or signal-enhancing modifications, could lead to a non-invasive, inexpensive diagnostic tool for population-wide screening of AD biomarkers in biological fluids other than CSF, such as serum or plasma.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Biosensing Techniques; Fluorescence; Humans; Immunoassay; Interferometry; Peptide Fragments; Polymers; Silicon; Silicon Dioxide

Aluminium (Al), a neurotoxin, has lately been implicated as one of the possible causal factors contributing to Alzheimer's disease. Because silicon (Si) intake can affect the bioavailability of aluminium, the object of the present study was to assess whether moderate beer consumption might, as a source of dietary Si, affect the toxicokinetics of Al and thereby limit that element's neurotoxicity. The results obtained confirmed that at moderately high levels of beer intake the Si present in the beer was able to reduce Al uptake in the digestive tract and thus was able to slow the accumulation of this metal in the body, brain tissue included. In consequence, moderate beer consumption, due to its content in bioavailability silicon, possibly affording a protective factor for preventing Alzheimer's disease, could perhaps be taken into account as a component of the dietary habits of the population.

Topics: Aluminum; Alzheimer Disease; Animals; Beer; Brain; Brain Chemistry; Feces; Growth; Male; Mice; Silicon; Spectrophotometry, Atomic; Weight Gain

The haematic concentration of 26 metals and the oxidative damage in 60 patients (20 males and 40 females) affected by Alzheimer's disease and 44 healthy individuals (33 males and 11 females) were compared. In patients, the following significant (p < or = 0.05) discrepancies were found: i) increment of Ca, Cd, Hg, Mg, Si and Sn, and decrement of Al, Co, Fe and Zn in serum; ii) higher concentrations of Cu, Li, Mn, Sn and Zr and lower of Fe, Hg, Mo in blood; iii) overproduction of oxidant species (SOS) and decrease of the anti-oxidant capacity (SAC) (p < or = 0.001, for both). Variables that, joined, better discriminated between patients and controls resulted to be Si, SOS, SAC, Co, Ca, Al in serum (94% of cases correctly classified) and Cu, Zr, Mo and Fe in blood (90% of cases properly categorized).

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Female; Humans; Hydrogen Peroxide; Lipid Peroxides; Male; Mass Spectrometry; Metals; Middle Aged; Oxidants; Oxidation-Reduction; Oxidative Stress; Silicon; Specimen Handling

There is a growing interest to evaluate metals in biological fluids in Alzheimer's disease (AD). There are numerous studies on this theme, but just few papers analyzed the relationship between haematic metal concentrations and the clinical features of the disease. In this study, possible associations between clinical features of AD and the variations in serum and blood concentration of some metals, as well as the serum oxidative status and the antioxidant capacity have been investigated. Sixty subjects with AD were enrolled. Some elements correlated with gender, depression and duration of the disease. However, the most significant result was the relationship between blood Ca and Fe levels and the severity of cognitive impairment. We hypothesize that Ca and Fe might play an important role in the pathogenetic mechanisms of AD.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Calcium; Female; Homeostasis; Humans; Iron; Male; Mass Spectrometry; Metals; Middle Aged; Neurofibrillary Tangles; Neuropsychological Tests; Oxidants; Silicon

Topics: Alzheimer Disease; Antioxidants; Diet; Dietary Supplements; Humans; Risk Factors; Silicon; Vitamin E

Metal ions play an important role in health and disease by influencing cellular biochemical pathways. The increased concentrations of some metal ions may have cytotoxic effects through their ability to oxidatively modify biomolecules, which may cause oxidative stress-induced brain cell death leading to neurodegenerative disorders observed in Alzheimer's disease (AD). We therefore performed elemental analysis of human brain tissues by a sophisticated method of inductively coupled plasma mass spectrometry (ICP-MS) in two regions of the AD brain, the parietal cortex and cerebellum, and compared them with the age-matched control. Our analysis shows the differential distribution of some metal ions in the two regions of the brain. Most importantly, Si, Sn, Al and Mn showed significantly higher levels in the parietal cortex of the AD brain compared to the control. The other metal ions showing moderate increases in the parietal cortex were Na, Te, Cr, Fe and B. Since these metal ions can modify lipoproteins in the brain and modified lipoproteins are taken up by scavenger receptors class B type I (SR-BI), we also determined the presence of SR-BI in the parietal cortex and cerebellum regions of the control and AD brains using a sensitive method, the reverse transcriptase-polymerase chain reaction. Our results suggest that SR-BI are present in the parietal cortex as well as in the cerebellum of the control and AD brains, suggesting that the presence of SR-BI may be involved in the uptake of oxidatively modified lipoproteins and beta-amyloid (Abeta) protein complexed with apoE, suggesting implications in the progression of late onset AD and other neurodegenerative disorders characterized by the deposition of insoluble aggregates observed in the AD brain.

Topics: Aged; Aged, 80 and over; Aluminum; Alzheimer Disease; CD36 Antigens; Cerebellum; Female; Humans; Ions; Lipoproteins; Manganese; Membrane Proteins; Metals; Oxidative Stress; Parietal Lobe; Reactive Oxygen Species; Receptors, Immunologic; Receptors, Lipoprotein; Receptors, Scavenger; Scavenger Receptors, Class B; Silicon; Superoxide Dismutase; Up-Regulation

Serum aluminium was significantly raised (p < 0.01) up to 2-3-fold, in patients with dementia including Alzheimers Disease (AD) 0.66 +/- 0.2 (mumol/l mean +/- 1 s.d.) and patients on regular aluminium hydroxide therapy 0.54 +/- 0.17, compared with healthy volunteers 0.21 +/- 0.13, although not as high as in patients with end stage renal failure on regular dialysis 0.88 +/- 0.42. The urine outputs (mumol/l mean +/- 1 s.d.) of aluminium and silicon, respectively, were also significantly increased up to 5-fold in dementia 2.89 +/- 1.78 (n = 23) and 1587 +/- 645 (n = 22) and patients on regular aluminium hydroxide therapy 5.03 +/- 2.08 (n = 8) and 998 +/- 364 (n = 21) compared with healthy volunteers 0.95 +/- 0.82 (n = 84) and 471 +/- 332 (n = 114). The increase in urine aluminium was thus associated with a similarly marked increase in the output of silicon. The increased absorption of aluminium in dementia patients is equivalent to the intestinal loading in Aludrox therapy. Also silicon appears to be important in the renal excretion of the absorbed aluminium. Whether this is a phenomenon related to the elderly or the process of dementia warrants further study.

Topics: Adult; Aged; Aged, 80 and over; Aging; Aluminum; Aluminum Hydroxide; Alzheimer Disease; Case-Control Studies; Dementia; Diet; Drug Combinations; Female; Humans; Intestinal Absorption; Kidney Failure, Chronic; Magnesium Hydroxide; Male; Middle Aged; Renal Dialysis; Silicon

In recent years, a possible relation between the aluminum and silicon levels in drinking water and the risk of Alzheimer disease (AD) has been established. It has been suggested that silicon may have a protective effect in limiting oral aluminum absorption. The present study was undertaken to examine the influence of supplementing silicon in the diet to prevent tissue aluminum retention in rats exposed to oral aluminum. Three groups of adult male rats were given by gavage 450 mg/kg/day of aluminum nitrate nonahydrate 5 days a week for 5 weeks. Concurrently, animals received silicon in the drinking water at 0 (positive control), 59, and 118 mg Si/L. A fourth group (-Al, - Si) was designated as a negative control group. At the end of the period of aluminum and silicon administration, urines were collected for 4 consecutive days, and the urinary aluminum levels were determined. The aluminum concentrations in the brain (various regions), liver, bone, spleen, and kidney were also measured. For all tissues, aluminum levels were significantly lower in the groups exposed to 59 and 118 mg Si/L than in the positive control group; significant reductions in the urinary aluminum levels of the same groups were also found. The current results corroborate that silicon effectively prevents gastrointestinal aluminum absorption, which may be of concern in protecting against the neurotoxic effects of aluminum.

Topics: Administration, Oral; Aluminum; Alzheimer Disease; Analysis of Variance; Animals; Bone and Bones; Brain; Male; Rats; Rats, Sprague-Dawley; Silicon; Viscera

To investigate the relation of aluminum and silicon in drinking water to risk of Alzheimer's disease, we carried out a case-control study in eight regions of England and Wales. Subjects were identified from the records of neuroradiology centers, and diagnoses were confirmed by a review of hospital case-notes. Exposure to aluminum and silicon in drinking water was estimated from residential histories of 106 men with Alzheimer's disease, 99 men with other dementing illnesses, 226 men with brain cancer, and 441 men with other diseases of the nervous system. All subjects in the study were between 42 and 75 years of age. There was little association between Alzheimer's disease and higher aluminum or lower silicon concentrations in drinking water when cases were compared with any of the control groups. The results indicate that any risk of Alzheimer's disease from aluminum in drinking water at concentrations below 0.2 mg per liter is small, and they give no support for a protective role of silicon.

Topics: Adult; Aged; Aluminum; Alzheimer Disease; Brain Neoplasms; Case-Control Studies; Dementia; England; Humans; Male; Middle Aged; Risk Factors; Silicon; Wales; Water Pollutants; Water Supply

Topics: Aging; Aluminum; Alzheimer Disease; Blood-Brain Barrier; Cytoplasmic Granules; Humans; Lipofuscin; Models, Biological; Neurofibrillary Tangles; Plaque, Amyloid; Risk Factors; Silicon

Topics: Alzheimer Disease; Amyloid beta-Peptides; Copper; Humans; Iron; Protein Binding; Silicon; Zinc

Aluminium and silicon are incidentally found in senile plaques (SP) and neurofibrillary tangles (NFT) of brains with Alzheimer's disease (AD), and have been considered as one of the risk factors for senile dementia. Since lipofuscin granules were concentrated concomitantly with SP and NFT in the high density fraction in subcellular fractionation of autopsied brains and are solid in nature, it was suspected that aluminum and silicon are accumulated in lipofuscin granules. Therefore, elemental analyses of partially purified lipofuscin granules from autopsied brains with AD and those without dementia, were attempted by energy dispersive X-ray spectrometry with a scanning electron microscope. It was demonstrated by a mapping method that aluminum and silicon were accumulated in some lipofuscin granules, probably as aluminosilicate. In addition, it was demonstrated by fluorescence microscopy of Bodian stained paraffin sections, that many SP and NFT contained lipofuscin granules, although lipofuscin granules were not always specific to those neuropathological changes. These results imply that aluminum detected in SP and NFT is due to lipofuscin granules and can explain the cause of discrepancies in the reports on the presence of aluminum in SP and NFT.

Topics: Aged; Aluminum; Alzheimer Disease; Female; Humans; Lipofuscin; Middle Aged; Nerve Degeneration; Neurofibrillary Tangles; Silicon; tau Proteins

Since lipofuscin granules were concentrated in the high density fraction in subcellular fractionation of autopsy brains of normal aged subjects and of patients with Alzheimer's disease (AD), it was suspected that inorganic materials accumulated in lipofuscin granules. Therefore, elemental analyses of clusters of lipofuscin granules in the high density fraction were attempted by energy dispersive X-ray spectrometry with a scanning electron microscope. It was demonstrated that aluminium (Al) and silicon (Si) accumulated in some lipofuscin granules. Al has been considered as one of risk factors of AD since Al and Si were found in senile plaques (SP) and neurofibrillary tangles (NFT) of the brains with AD, although conflicting results also have been reported. It was also demonstrated in this experiment by fluorescence microscopy of Bodian stained paraffin sections of AD brain that many SP and NFT contained lipofuscin granules, although lipofuscin granules were not always specific to those neuropathological changes. The results of this experiment imply that Al detected in SP and NFT is contained in lipofuscin granules.

Topics: Aged; Aged, 80 and over; Aluminum; Alzheimer Disease; Autopsy; Brain; Female; Humans; Lipofuscin; Male; Microscopy, Fluorescence; Middle Aged; Silicon

The possible involvement of environmental aluminum in the etiology of Alzheimer disease and of senile dementia of the Alzheimer type is supported by both direct and indirect relationships between some encephalopathies and the abnormal presence of aluminum(III) in human and animal brain tissues. Proposals for further biochemical, toxicological and analytical work are illustrated.

Topics: Aluminum; Alzheimer Disease; Humans; Silicon

We designed a prospective study to determine whether CSF silicon elevation is specific for Alzheimer-type dementia (ATD) and whether it is related to the severity of cognitive or functional impairment. We found elevated CSF silicon in 30% of 23 ATD patients but in only 1 of the 23 age-matched nondemented controls. In all ATD patients with elevated CSF silicon, symptoms began after age 65. Thirty-four percent of 29 patients with other types of dementia also had elevated CSF silicon. Therefore, elevated CSF silicon concentrations are not specific for ATD, but they correlate with age and severity of functional impairment in late-onset ATD.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Dementia; Humans; Middle Aged; Prospective Studies; Silicon

Using inductively coupled argon plasma emission spectroscopy, we measured 19 trace elements in cerebrospinal fluid of 265 patients who were undergoing diagnostic lumbar puncture. Thirty-three patients had Alzheimer-type dementia (ATD); 16 patients had other dementing illnesses; and 20 had no neurologic disease. There were seven cases of autopsy-proven Alzheimer's disease (AD) and eight autopsy controls. We found elevated CSF silicon in 24% of ATD and 71% of AD patients. We found no relationship between CSF aluminum, arsenic, lead, or manganese and ATD, AD, or other dementing illnesses.

Topics: Aged; Alzheimer Disease; Dementia; Female; Humans; Male; Middle Aged; Silicon; Trace Elements; Zinc

The elemental content of neurons of the hippocampus was studied by a combination of scanning electron microscopy and x-ray spectrometry in autopsy-derived brain tissue from three cases of senile dementia (Alzheimer type) and three nondemented elderly controls. Foci of aluminum were detected within the nuclear region of a high percentage of neurons containing neurofibrillary tangles from the cases of senile dementia as well as the elderly controls. The adjacent normal-appearing neurons from both groups of patients were virtually free of detectable aluminum. These findings suggest that the association of aluminum to Alzheimer's disease extends to the neuronal level.

Topics: Aluminum; Alzheimer Disease; Cell Nucleus; Dementia; Electron Probe Microanalysis; Hippocampus; Humans; Magnesium; Microscopy, Electron, Scanning; Neurofibrils; Silicon

Electron probe microanalysis demonstrates the presence of aluminum, calcium, phosphorus and silica in senile plaques in the cerebral cortex of 4 patients. Our findings are reported here with the reservation tnat the tissues were fixed before examination.

Topics: Aluminum; Alzheimer Disease; Brain; Brain Chemistry; Calcium; Dementia; Humans; Microscopy, Electron; Phosphorus; Silicon

Topics: Aged; Aging; Alzheimer Disease; Body Fluids; Brain; Dementia; Female; Humans; Kidney; Liver; Male; Middle Aged; Myocardium; Nails; Silicon; Spleen