Aluminum Levels in Brain, Serum, and Cerebrospinal Fluid are Higher in Alzheimer's Disease Cases than in Controls: A Series of Meta-Analyses

Background: Aluminum is the most studied environmental agent linked with Alzheimer's disease (AD). However, it remains unclear whether levels are significantly elevated in AD sufferers. Objective: To systematically assess levels of aluminum in brain, serum, and cerebrospinal fluid (CSF) of AD cases and controls. Methods: Electronic searches of Medline, Embase, PubMed, and Cochrane Library were conducted up to June 2015. Studies reporting brain, serum, or CSF aluminum levels in individuals with AD and non-demented controls were included. Meta-analyses were performed using random-effects models and the pooled standardized mean difference (SMD) reported with 95% confidence intervals (CI). Results: Overall, 34 studies involving 1,208 participants and 613 AD cases met the criteria for inclusion. Aluminum was measured in brain tissue in 20 studies (n = 386), serum in 12 studies (n = 698), and CSF in 4 studies (n = 124). Compared to control subjects, AD sufferers had significantly higher levels of brain (SMD 0.88; 95% CI, 0.25-1.51), serum (SMD 0.28; 95% CI, 0.03-0.54), and CSF (SMD 0.48; 95% CI, 0.03-0.93) aluminum. Sensitivity analyses excluding studies without age-matched controls did not impact upon these results. Conclusions: The findings of the present meta-analyses demonstrate that aluminum levels are significantly elevated in brain, serum, and CSF of patients with AD. These findings suggest that elevated aluminum levels, particularly in serum, may serve as an early marker of AD and/or play a role in the development of the disease. These results substantially clarify the existing evidence examining the link between chronic aluminum exposure and the development of AD.