Brain alpha-amylase: a novel energy regulator important in Alzheimer disease?

Reduced glucose metabolism and formation of polyglucosan bodies (PGB) are, beside amyloid beta plaques and neurofibrillary tangles, well-known pathological findings associated with Alzheimer's disease (AD). Since both glucose availability and PGB are regulated by enzymatic degradation of glycogen, we hypothesize that dysfunctional glycogen degradation is a critical event in AD progression. We therefore investigated whether alpha (alpha)-amylase, an enzyme known to efficiently degrade polysaccharides in the gastrointestinal tract, is expressed in the hippocampal CA1/subiculum and if the expression is altered in AD patients. Using immunohistochemical staining techniques, we show the presence of the alpha-amylase isotypes AMY1A and AMY2A in neuronal dendritic spines, pericytes and astrocytes. Moreover, AD patients showed reduced gene expression of alpha-amylase, but conversely increased protein levels of alpha-amylase as well as increased activity of the enzyme compared with non-demented controls. Lastly, we observed increased, albeit not significant, load of periodic acid-Schiff positive PGB in the brain of AD patients, which correlated with increased alpha-amylase activity. These findings show that alpha-amylase is expressed and active in the human brain, and suggest the enzyme to be affected, alternatively play a role, in the neurodegenerative Alzheimer's disease pathology.