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Cited by 509Alzheimer's disease research and treatmentsAluminum toxicity and tolerance in plants and animalsDementia and Cognitive Impairment Research

Link between Aluminum and the Pathogenesis of Alzheimer′s Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses

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Kawahara, Masahiro, Kato-Negishi, Midori·2011·International Journal of Alzheimer’s Disease
DOI 10.4061/2011/276393PMC PMC3056430
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Abstract

Whilst being environmentally abundant, aluminum is not essential for life. On the contrary, aluminum is a widely recognized neurotoxin that inhibits more than 200 biologically important functions and causes various adverse effects in plants, animals, and humans. The relationship between aluminum exposure and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii Peninsula and Guam, and Alzheimer′s disease (AD) has been suggested. In particular, the link between aluminum and Alzheimer′s disease has been the subject of scientific debate for several decades. However, the complex characteristics of aluminum bioavailability make it difficult to evaluate its toxicity and therefore, the relationship remains to be established. Mounting evidence has suggested that significance of oligomerization of β ‐amyloid protein and neurotoxicity in the molecular mechanism of AD pathogenesis. Aluminum may play crucial roles as a cross‐linker in β ‐amyloid oligomerization. Here, we review the detailed characteristics of aluminum neurotoxicity based on our own studies and the recent literatures. Our aim is to revisit the link between aluminum and AD and to integrate aluminum and amyloid cascade hypotheses in the context of β ‐amyloid oligomerization and the interactions with other metals.

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  • In humans, Al accumulation in the brain and scalp hairs has been associated with neurodegenerative diseases such as dialysis-associated encephalopathy, Alzheimer's disease, Parkinson's disease (dementia), amyotropic lateral sclerosis, multiple sclerosis and autism.

    “In humans, Al accumulation in the brain and scalp hairs has been associated with neurodegenerative diseases such as dialysis-associated encephalopathy, Alzheimer’s disease, Parkinson’s disease (dementia), amyotropic lateral sclerosis, multiple sclerosis and autism (King et al., 1981; Savory et al., 1996; Kawahara and Kato-Negishi, 2011; Arain et al., 2015; Jones et al., 2017; Mirza et al., 2017;”

    From Aluminium toxicosis: a review of toxic actions and effects (2019) · cites this paper as Kawahara and Kato-Negishi, 2011

    The Introduction links aluminum to Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinsonism dementia; §§2.1 and 3.1 also describe dialysis encephalopathy, and §3.2 reports aluminum in Alzheimer’s brain tissue. These passages do not support the claim about scalp-hair accumulation or associations with multiple sclerosis and autism. The paper also describes the disease links as suspected rather than established. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Kawahara, M., & Kato-Negishi, M.
Affiliations
Kyushu University of Medical Science (JP)
Corresponding author
Kawahara, Masahiro
ORCID
Kawahara, Masahiro
Venue
International Journal of Alzheimer’s Disease
Publisher
Wiley
Published
2011-01
Volume
2011
Issue
1
Pages
276393-276393
ISSN
  • 2090-0252 (ISSN-L)
  • 2090-8024
DOI
10.4061/2011/276393
PMC
PMC3056430
OpenAlex
W2047667409
Cited by
509
References
6
Citations by year
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FWCI
15.06
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Alzheimer s Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Education, Culture, Sports, Science, and Technology
  • Miyazaki Prefectural Industrial Support Foundation
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
aluminum, Alzheimer's disease, amyloid hypothesis, aluminum neurotoxicity, metal interactions, neurodegenerative diseases, dialysis encephalopathy, Guam

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