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The first successful attempt to obtain purified aluminum metal was accomplished by the Danish physicist and chemist Hans Christian Orsted in 1824, however it was not until about ~140 years later that aluminum's capacity for neurological disruption and neurotoxicity was convincingly established. The earliest evidence of the possible involvement of this biosphere-rich metallotoxin in Alzheimer's disease (AD) originated in the early-to-mid-1960's from animal and human research investigations that arose almost simultaneously from independent laboratories in the United States and Canada. This short communication pays tribute to the pioneering research work on aluminum in susceptible species, in AD animal models and in AD patients by the early investigators Drs. Robert D. Terry, Igor Klatzo and Henryk M. Wisniewski with special acknowledgement to the late Dr. Donald RC McLachlan, and their contemporary physician-scientist colleagues and collaborators. Together these researchers established the groundwork and foundation towards our understanding of the potential contribution of aluminum to progressive, age-related and lethal neurodegenerative diseases of the human central nervous system., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.) more...

Gram-negative bacteria of the human gastrointestinal (GI) tract microbiome: (i) are capable of generating a broad-spectrum of highly neurotoxic, pro-inflammatory and potentially pathogenic molecules; and (ii) these include a highly immunogenic class of amphipathic surface glycolipids known as lipopolysaccharide (LPS). Bacteroides fragilis (B. fragilis), a commensal, Gram negative, non-motile, non-spore forming obligatory anaerobic bacillus, and one of the most abundant bacteria found in the human GI tract, produces a particularly pro-inflammatory and neurotoxic LPS (BF-LPS). BF-LPS: (i) is known to be secreted from the B. fragilis outer membrane into the external-medium; (ii) can damage biophysiological barriers via cleavage of zonula adherens cell-cell adhesion proteins, thereby disrupting both the GI-tract barrier and the blood-brain barrier (BBB); (iii) is able to transit GI-tract barriers into the systemic circulation and cross the BBB into the human CNS; and (iv) accumulates within CNS neurons in neurodegenerative disorders such as Alzheimer's disease (AD). This short communication provides evidence that the incubation of B. fragilis with aluminum sulfate [Al 2 (SO 4 ) 3 ] is a potent inducer of BF-LPS. The results suggest for the first time that the pro-inflammatory properties of aluminum may not only be propagated by aluminum itself, but by a stimulation in the production of microbiome-derived BF-LPS and other pro-inflammatory pathogenic microbial products normally secreted from human GI-tract-resident microorganisms., Competing Interests: Declaration of competing interest Declaration of interest for all authors including financial and personal relationships with other people or organizations: none. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. This work was reviewed and approved by the Institutional Biosafety Committee/Institutional Review Board (IBC/IRB) at the LSU Health Sciences Center, New Orleans LA 70112 USA., (Published by Elsevier Inc.) more...

IgG subclasses were measured in sera from 33 persons with Down syndrome (DS) (mean age 55 +/- 7 years) and 33 age- and sex-matched control individuals using a mouse monoclonal antibody based sandwich enzyme linked immunosorbent assay. Significantly higher levels of IgG1 and IgG3 and lower levels of IgG2 and IgG4 subclasses were found in the DS group compared to the control individuals. The higher levels of IgG1 and IgG3 subclasses found in DS persons were consistent with those seen in patients with autoimmune diseases and chronic viral infections; the lower levels of IgG2 and IgG4 subclasses were consistent with those seen in patients with recurrent infections. Our findings are similar to those reported in children with DS. We speculate that the subclass levels may have little or no relationship to the development of brain lesions typical of Alzheimer disease in older persons with DS. There were no significant differences between the levels of IgG subclasses of persons with DS showing signs of dementia of the Alzheimer type compared to those without such manifestations. more...