The putative role of environmental aluminium in the development of chronic neuropathology in adults and children. How strong is the evidence and what could be the mechanisms involved?
Authors: Richard E Frye
Gerwyn Morris
Basant K Puri
Journal: Metabolic brain disease (2017)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Aluminum; Alzheimer disease; Autism spectrum disorder; Autoimmunity; Brain
Affiliations: Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA15 2LW, UK., Department of Medicine, Imperial College London, Hammersmith Hospital, London, England, W12 0HS, UK. ., College of Medicine, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR, 72202, USA.

Abstract:  The conceptualisation of autistic spectrum disorder and Alzheimer's disease has undergone something of a paradigm shift in recent years and rather than being viewed as single illnesses with a unitary pathogenesis and pathophysiology they are increasingly considered to be heterogeneous syndromes with a complex multifactorial aetiopathogenesis, involving a highly complex and diverse combination of genetic, epigenetic and environmental factors. One such environmental factor implicated as a potential cause in both syndromes is aluminium, as an element or as part of a salt, received, for example, in oral form or as an adjuvant. Such administration has the potential to induce pathology via several routes such as provoking dysfunction and/or activation of glial cells which play an indispensable role in the regulation of central nervous system homeostasis and neurodevelopment. Other routes include the generation of oxidative stress, depletion of reduced glutathione, direct and indirect reductions in mitochondrial performance and integrity, and increasing the production of proinflammatory cytokines in both the brain and peripherally. The mechanisms whereby environmental aluminium could contribute to the development of the highly specific pattern of neuropathology seen in Alzheimer's disease are described. Also detailed are several mechanisms whereby significant quantities of aluminium introduced via immunisation could produce chronic neuropathology in genetically susceptible children. Accordingly, it is recommended that the use of aluminium salts in immunisations should be discontinued and that adults should take steps to minimise their exposure to environmental aluminium. 

Retracted: No

PubPeer comments:
 The authors adduce the MMR vaccine as evidence for their argument that vaccine adjuvants (and other forms of environmental aluminium) cause neuropathy:  *There is a vast body of data demonstrating that immune and inflammatory responses to vaccines such as **MMR** are heavily influenced by polymorphisms in the HLA region and in genes encoding effector proteins such as cytokines and PRRs which have the capacity to recognise and become activated by conserved pathogen-associated molecular patterns (PAMPs) to produce immune response molecules such as PICs and interferons (Haralambieva et al. 2013; Lucas and Maes 2013).* MMR vaccine does not contain aluminium adjuvants.  *Readers interested in examining the evidence purporting to demonstrate an association between HLA polymorphisms and unusual response to the **MMR** vaccine are referred to an excellent review by Castiblanco and Anaya 2015.* Castiblanco and Anaya (2015) do not mention *unusual* response to the MMR vaccine, just the *normal range* of responses. I have no idea how the authors get onto the topic of **mercury**: ![file] Perhaps it fell in from their parallel paper on [ The Putative Role of Environmental Mercury in the Pathogenesis and Pathophysiology of Autism Spectrum Disorders and Subtypes ] . ,