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

Elin Byman,Nina Schultz,Malin Fex,Malin Wennström,Netherlands Brain Bank

doi:10.1111/bpa.12597

Abstract

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 (α)‐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 α‐amylase isotypes AMY1A and AMY2A in neuronal dendritic spines, pericytes and astrocytes. Moreover, AD patients showed reduced gene expression of α‐amylase, but conversely increased protein levels of α‐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 α‐amylase activity. These findings show that α‐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.

Highlights

Alzheimer’s disease (AD) is neuropathologically characterized by amyloid beta (Ab)42 plaques and neurofibrillary tangles (NFT) [8]
To confirm that the amylase 1A (AMY1A) staining was associated with neuronal processes, we double stained the sections against AMY1A and the neurofilament light chain (NFTL)
Further double immunofluorescence staining showed that many of the AMY1A positive Hirano bodies (HB) in AD patients were associated with plaques positive for Ab (Figure 1F) and co-localized with p-tau positive tangles (Figure 1G)

Summary

Introduction

Alzheimer’s disease (AD) is neuropathologically characterized by amyloid beta (Ab) plaques and neurofibrillary tangles (NFT) [8] These hallmarks of AD are closely related to the synaptic/neuronal loss and cognitive decline [25] associated with the disease. Glycogen is a highly multibranched polysaccharide consisting of linear glucose chains linked together with alpha (a)(1–4) glyosidic bonds and chains branching off by a(1–6) glyosidic bonds [1, 11]. It is synthesized by brain specific glycogen synthetase [34] and found foremost in the cytosol of astrocytes, and in endothelial cells, pericytes and neurons [12].

Methods

Results

Conclusion