Aluminum induces tau aggregation in vitro but not in vivo.
Etiological studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer's disease (AD). Biochemical analysis data on the effects of Al, however, are inconsistent. Hence, the pathological involvement of Al in AD remains unclear. If Al is involved in AD, then it is reasonable to hypothesize that Al might be involved in the formation of either amyloid plaques or neurofibrillary tangles (NFTs). Here, we investigated whether Al might be involved in NFT formation by using an in vitro tau aggregation paradigm, a tau-overexpressing neuronal cell line (N2a), and a tau-overexpressing mouse model. Although Al induced tau aggregation in a heparin-induced tau assembly assay, these aggregates were neither thioflavin T positive nor did they resemble tau fibrils seen in human AD brains. With cell lysates from stable cell lines overexpressing tau, the accumulation of SDS-insoluble tau increased when the lysates were treated with at least 100 muM Al-maltolate. Yet Al-maltolate caused illness or death in transgenic mice overexpressing human tau and in non-transgenic littermates well before the Al concentration in the brain reached 100 muM. These results indicate that Al has no direct link to AD pathology.
Laboratory for Alzheimer Disease, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
Tatsuya
T
Mizoroki
Shunsuke
S
Meshitsuka
Sumihiro
S
Maeda
Miyuki
M
Murayama
Naruhiko
N
Sahara
Akihiko
A
Takashima
D000535:Aluminum / Q000493:pharmacokinetics / Q000633:toxicity*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D011753:Pyrones / Q000493:pharmacokinetics / Q000633:toxicity; D013050:Spectrometry, Fluorescence; D016875:tau Proteins / Q000187:drug effects* / Q000235:genetics
D017607:Aluminum Compounds; D002712:Chlorides; D009942:Organometallic Compounds; D011753:Pyrones; D016875:tau Proteins; C067527:aluminum maltolate; D000077410:Aluminum Chloride; D000535:Aluminum