Alzheimer ́s disease (AD) is a complex neurodegenerative disease characterized by progressive destruction of mainly brain cortical areas related to cognitive and memory performances. Most identified forms of AD are idiopathic and the precise pathogenic mechanisms remain yet unknown. Neuropathological hallmarks of AD include amyloid plaques and neurofibrillary tangles whose development correlate with neuronal death. At present, there is evidence that factors other than aging and genetic prone to develop AD contribute as cofactors in neuropathological cascades. Aluminum is considered a neurotoxic metal for humans. Some previous studies have revealed the accumulation of aluminum in the cerebral parenchyma of postmortem brains of patients suffering AD. In this study, we show that aluminum is present in significant amounts in the cerebrospinal fluid (CSF) of control healthy individuals and that its concentration increases in individuals with AD. Aluminum in CSF is also elevated in patients with mild cognitive impairment (MCI), considered to be a prodromal stage of AD. Aluminum contents correlate with classical biomarkers of AD (particularly with phosphorylated tau and amyloid β) following complex association patterns which vary depending on the stage of the AD spectrum, and dismiss a direct relationship. Associated with increased aluminum in AD patients, indicators of oxidative stress, namely Iso-PG2 and MDA, are also increased in the CSF of AD and MCI individuals, which also correlate with aluminum concentration. We hypothesize that aluminum content in CSF is a significant factor which, in synergy with other variables, may favors the initiation and progression of AD.
