Журнал болезни Альцгеймера и паркинсонизма

Абстрактный

Aluminum and Alzheimer ' s Disease: An Update

Yasumasa Ohyagi and Katsue Miyoshi

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.