Aluminium detected in senile plaques and neurofibrillary tangles is contained in lipofuscin granules with silicon, probably as aluminosilicate

Tokutake, Satoshi; Nagase, Hirokazu; Morisaki, Shigeyoshi; Oyanagi, Shinsaku

doi:10.1016/0304-3940(94)11234-a

Cited by 52 publications

(29 citation statements)

References 22 publications

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“…Aluminum and Si were codeposited in the vacuoles of the expanding root cortical cells after exposure to Al for 24 h (38). Equivalent vacuolar codeposition of Al and Si in the human brain with Alzheimer's disease is suggested by data on the inorganic content of isolated lipofuscin granules, which are lysosomal degradation products (39,40). It is possible, therefore, that vacuolar͞lysosomal codeposition of Si and Al is a conserved mechanism in plants and animals, which, based upon the findings here, would represent a specific mechanism for detoxification of Al through the upregulation of intracellular Si.…”

Section: Lability Of Polyhydroxy Aluminum In the Presence Andsupporting

confidence: 53%

Aluminum-dependent regulation of intracellular silicon in the aquatic invertebrate Lymnaea stagnalis

Desouky¹,

Jugdaohsingh²,

McCrohan³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Silicon is essential for some plants, diatoms, and sponges but, in higher animals, its endogenous regulation has not been demonstrated. Silicate ions may be natural ligands for aluminum and here we show that, in the freshwater snail (Lymnaea stagnalis), intracellular silicon seems specifically up-regulated in response to sublethal aluminum exposure. X-ray microanalysis showed that exposure of snails to low levels of aluminum led to its accumulation in lysosomal granules, accompanied by marked up-regulation of silicon. Increased lysosomal levels of silicon were a specific response to aluminum because cadmium and zinc had no such effect. Furthermore, intra-lysosomal sulfur from metallothionein and other sulfur-containing ligands was increased after exposure to cadmium and zinc but not aluminum. To ensure that these findings indicated a specific in vivo response, and not ex vivo formation of hydroxy-aluminosilicates (HAS) from added aluminum (555 g͞ liter) and water-borne silicon (43 g͞liter), two further studies were undertaken. In a ligand competition assay the lability of aluminum (527 g͞liter) was completely unaffected by the presence of silicon (46 g͞liter), suggesting the absence of HAS. In addition, exogenous silicon (6.5 mg͞liter), added to the water column to promote formation of HAS, caused a decrease in lysosomal aluminum accumulation, showing that uptake of HAS would not explain the loading of aluminum into lysosomal granules. These findings, and arguments on the stability, lability, and kinetics of aluminum-silicate interactions, suggest that a silicon-specific mechanism exists for the in vivo detoxification of aluminum, which provides regulatory evidence of silicon in a multicellular organism.

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Section: Lability Of Polyhydroxy Aluminum In the Presence Andsupporting

confidence: 53%

Aluminum-dependent regulation of intracellular silicon in the aquatic invertebrate Lymnaea stagnalis

Desouky¹,

Jugdaohsingh²,

McCrohan³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…A typical neuritic plaque consists of a central core of extracellular amyloid fibrils intermingled with and surrounded by abnormal neuronal processes (4,5). Some neuritic plaques are known to contain metal particles, such as iron (6,7).…”

mentioning

confidence: 99%

Detection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy

Benveniste

Einstein

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

224

168

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Magnetic resonance microscopy (MRM) theoretically provides the spatial resolution and signal-to-noise ratio needed to resolve neuritic plaques, the neuropathological hallmark of Alzheimer's disease (AD). Two previously unexplored MR contrast parameters, T2* and diffusion, are tested for plaque-specific contrast to noise. Autopsy specimens from nondemented controls (n ‫؍‬ 3) and patients with AD (n ‫؍‬ 5) were used. Three-dimensional T2* and diffusion MR images with voxel sizes ranging from 3 ؋ 10 ؊3 mm 3 to 5.9 ؋ 10 ؊5 mm 3 were acquired. After imaging, specimens were cut and stained with a microwave king silver stain to demonstrate neuritic plaques. From controls, the alveus, fimbria, pyramidal cell layer, hippocampal sulcus, and granule cell layer were detected by either T2* or diffusion contrast. These structures were used as landmarks when correlating MRMs with histological sections. At a voxel resolution of 5.9 ؋ 10 ؊5 mm 3 , neuritic plaques could be detected by T2*. The neuritic plaques emerged as black, spherical elements on T2* MRMs and could be distinguished from vessels only in cross-section when presented in three dimension. Here we provide MR images of neuritic plaques in vitro. The MRM results reported provide a new direction for applying this technology in vivo. Clearly, the ability to detect and follow the early progression of amyloid-positive brain lesions will greatly aid and simplify the many possibilities to intervene pharmacologically in AD.

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“…The yield of HDF from AD brain was 100-200 ¿¿g in dry weight and less than 100 /zg from the normal aged brain [2,3,4].…”

Section: Autopsy Brainsmentioning

confidence: 99%

“…They are contained more abundantly in the brain with senile dementia and AD [1], but are not always charac teristic neuropathological features unlike SP and NFT. Since lipofuscin granules and corpora amylacea were concentrated with SP and NFT in the high density fraction in subcellular fractionation of autopsy brain with AD [2,3,4] and are solid in nature, it was suspected that inorganic materials accumulated in lipofuscin granules and corpora amylacea. In addition, since many reports have demonstrated the pres ence of A1 and Si in SP [5] and NFT [6,7,8,9], A1 has been suspected as one of etio logical factors of senile dementia and AD [10,11,12], although conflicting results were also reported [13,14,15].…”

Section: Introductionmentioning

confidence: 99%

Accumulation of Aluminium and Silicon in Lipofuscin Granules

Tokutake¹,

Oyanagi

1995

Gerontology

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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.

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Aluminium detected in senile plaques and neurofibrillary tangles is contained in lipofuscin granules with silicon, probably as aluminosilicate

Cited by 52 publications

References 22 publications

Aluminum-dependent regulation of intracellular silicon in the aquatic invertebrate Lymnaea stagnalis

Aluminum-dependent regulation of intracellular silicon in the aquatic invertebrate Lymnaea stagnalis

Detection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy

Accumulation of Aluminium and Silicon in Lipofuscin Granules

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