Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity
Authors: C A Shaw
L Tomljenovic
Journal: Immunologic research (2013)
Discipline: IMMUNOLOGY
Keywords: neurotoxicity; aluminum; nervous system; Alzheimer's; ALS-PDC
Affiliations: Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia (UBC), 828 W. 10th Ave., Vancouver, BC, V5Z 1L8, Canada. 

Abstract:  We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome. 

Retracted: No

PubPeer comments:
  The cause of the disorder in Guam was eventually narrowed down to various putative environmental toxins, including toxins from the seed of the cycad palm which the Chamorro people once frequently ate, and **abnormally high aluminum in the soil and water in southern Guam [25]**. These data remain controversial but clearly point to a potential link between aluminum and ALS. Reference [25] is Intraneuronal deposition of calcium and aluminum in amyotrophic lateral sclerosis of Guam [(Garruto et al, 1985)] 92642-X fulltext). Garruto et al say **nothing** about  abnormally high aluminum in the soil and water in southern Guam , instead proposing that the accumulations they reported were a *symptom* of a metabolic problem rather than a cause.  [...T]he hypothesis that these neurodegenerative diseases result from a basic defect in mineral metabolism which ultimately impairs axonal transport of neurofilament proteins . , 
 Garruto worked with Gadjusek who basically postulated the high Al content led to the dysregulation of Ca Mg. Steele looked at various soil and water samples in south Guam and did not find high levels. Hence, the issue remains quite uncertain. , 
 #2 I think the concern may be that the citation [25] does not appear to support the statement it follows, which may confuse readers. I agree with #1 that the Lancet letter makes no mention of soil and water conditions in Southern Guam. Perhaps you can provide a suitable replacement citation that supports your reply in #2. , 
 #2  Garruto worked with Gadjusek who basically postulated the high Al content led to the dysregulation of Ca Mg. Could you clarify where Gadjusek postulated this theory? All I have read are papers like  Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam (Garruto, Yanagihara, Gajdusek 1985), where the hypothesis is that  the previously high incidence resulted from defects in mineral metabolism and secondary hyperparathyroidism, provoked by nutritional deficiencies of calcium and magnesium, with resultant deposition of calcium and aluminum in neurons . IOW dysregulation comes first, with Al accumulation as a **result**. In 1995, Garruto described his hypothesis as  that a basic defect in mineral metabolism induces a form of secondary hyperparathyroidism, provoked by chronic nutritional deficiencies of calcium and magnesium leading to enhanced gastrointestinal absorption of bioactive aluminum and the deposition of calcium and silicon as hydroxyapatites or aluminosilicates in neurons. It sounds as if that group had come to emphatically reject any suggestion of abnormal *exposure* to Al as a cause of ALS in Guam, so it s strange to cite them in **support** of that suggestion. , 
 Gajdusek (note the spelling of the name, the J comes before the D) actually co-authored a paper that said as much *10 years earlier*. Garruto, Ralph M., Richard Yanagihara, and D. Carleton Gajdusek. [ Disappearance of highu2010incidence amyotrophic lateral sclerosis and parkinsonismu2010dementia on Guam. ] Neurology 35.2 (1985): 193-193. Abstract: *The high incidence rates of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) occurring among the Chamorros of Guam have declined to rates only slightly higher than those observed in the continental United States. This decline has occurred principally among males, especially those born after 1920 and **living in areas where calcium and magnesium levels are low in soil and water.** The male-to-female ratio among affected patients now approaches unity, compared with ratios of 2 to 1 for ALS and 3 to 1 for PD three decades ago. **These changes are consistent with the hypothesis that the previously high incidence resulted from defects in mineral metabolism and secondary hyperparathyroidism, provoked by nutritional deficiencies of calcium and magnesium, with resultant deposition of calcium and aluminum in neurons.*** There was clearly a misunderstanding and a mis-citation on the part of Shaw and Tomljenovic. Yes, according to this hypothesis, there is  deposition of calcium and aluminum in neurons as part of the problem, and that may in some way give credence to the notion of aluminum as a neurotoxin. But it isn t because of excessive aluminum in the soil and water. That part is a misunderstanding. EDIT: Taking a closer look, I see that #4 mentioned this same article. I still think it worthwhile to post a link and the abstract in full, because it mentions that the soil is low in calcium and magnesium, but it doesn t mention aluminum. I also think it s worth emphasizing that aluminum is still a neurotoxic agent in this scenario. ,