Epidemiological studies indicate that alcohol consumption is associated with a lower risk of Alzheimer Disease (AD); however, the potential benefits may vary due to genetics, health history, and the amount or type of alcohol consumed.1-16 Conversely, the available data also show that excessive alcohol drinking is associated with a higher risk of AD, and that genotype modifies this association.3, 7,17-19
In line with epidemiological reports, neurobiological findings indicate that the association between alcohol consumption and AD is complex, but molecular mechanisms underlying both protective and damaging effects of alcohol are being illuminated.20-28
Moderate consumption of red wine, for example, attenuates amyloid-beta neuropathology, as well as the concomitant spatial memory deficits in a mouse model of AD.24 Also, moderate ethanol (EtOH) preconditioning inhibits amyloid-beta-induced neurotoxicity in hippocampal slices.21 Closely related, low concentrations of EtOH protect cultured hippocampal neurons against amyloid-beta-induced synapse damage,20,22 and EtOH reduces amyloid aggregation in vitro, and prevents toxicity in HEK and PC12 cells.23
On the contrary, the expression of amyloid-beta precursor protein (APP) and beta-secretase (BACE1) is increased in both the hippocampus and striatum of rats fed an alcohol liquid diet for 5 weeks.26 Also, withdrawal from exposure to a high concentration of EtOH produces significant cellular injury in the CA1 subregion of the hippocampus.28 Related to these findings, alcohol enhances amyloid-beta-induced neuronal cell death by increasing reactive oxygen species (ROS) production, and EtOH enhances tau accumulation in neuroblastoma cells that inducibly express tau.25
It is well established that thiamine deficiency is associated with both chronic alcoholism and AD-related pathology, and both human and rodent studies confirm a role of thiamine in AD.29-37 More specifically, plasma thiamine deficiency is associated with AD in humans33, and reduced activity of thiamine-dependent enzymes is found in the brains of patients who were diagnosed with AD.38 Also, thiamine deficiency is associated with increased beta-amyloid production in cultured neuronal cells,36 with increased beta-amyloid accumulation in the brains of wild-type mice,36,37 and with amyloid plaque formation in AD transgenic mice.37,39
Although thiamine supplementation may reverse AD-related pathologies in rodents,36 clinical trials to date provide inconsistent evidence for beneficial effects of thiamine supplementation in humans diagnosed with AD.40,41
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