Aluminium and Alzheimer's disease--an update.

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. AD is characterized by senile plaques and neurofibrillary tangles (NFTs) comprised of amyloid-β protein (Aβ) deposits and hyper-phosphorylated tau protein (p-tau), respectively. Oxidative stress-induced neuronal damage is also involved in AD pathogenesis. In the 1970s, studies showed increased levels of aluminum (Al) in the AD brain, and neurofibrillary changes upon its injection into the brain, thus leading to the suggestion that Al may be one of the major causes of AD. However, later reports contradicted this hypothesis as studies revealed that Al-induced neurofibrillary changes were different from NFT sin AD, and intake of high dose Al-containing antacid drugs did not induce AD. Other in vitro and in vivo studies found that Al was neurotoxic, and possibly promoting aggregation of Aβ and p-tau. Here, we review and verify the validity of Al pathogenesis in AD. Despite the multitude of studies, no direct evidence currently exists that specifically links Al with AD pathogenesis. Therefore, more advanced cohort studies are necessary to better understand the absolute risk of Al for AD, and to rigorously compare this link using other neurotoxic metals. Taken together, Al may be an environmental factor promoting cognitive impairment in AD patients, as well as other free radical-generating metal ions such as iron, copper and zinc. By the 1970s, the association between Al and AD pathogenesis became a major topic of scientific discussion. Crapper and Dalton reported that administration of Al into cat brain induced memory impairment and neurofibrillary degeneration [15]. Increased levels of Al were documented in AD brain tissues [16-18]; however, these elevations were later found to be associated with aging and not with NFT levels [19]. Numerous studies have provided varying results (despite the use of similar methods) when measuring the levels of Al in human brain tissues, found to be both positive (Table 1) and negative (Table 2). Although the exact reason for these discrepancies is unclear, differences in the sample tissues may have been a factor. Indeed, since aging may increase Al levels in the brain [19], selection of age-matched control brain tissues may thus be important. Al was also suggested to be the cause of dialysis-associated encephalopathy (DAE) [20,21]. However, the DAE pathology was found to be clearly different from AD pathology (for more information, see below). Thus, in the following years, the debate about association between Al and AD diminished. Epidemiology of Al and AD Contamination of drinking water with Al polychloride in Camelford, England (Camelford water pollution incident; 1988) occurred. It was later revealed that the prevalence of dementia was not increased [22]. While, it was reported that the prevalence of AD was 1.5-fold higher in the area with water containing Al over 0.11 mg/L compared with the area of water containing Al under 0.01 mg/L [23]. Citation: Ohyagi Y, Miyoshi K (2013) Aluminum and Alzheimer’s Disease: An Update. J Alzheimers Dis Parkinsonism 3: 118. doi:10.4172/21610460.1000118