Brain alpha-amylase : a novel energy regulator important in Alzheimer disease?
(2018) In Brain Pathology 28(6). p.920-932- 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... (More)
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.
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- author
- Byman, Elin LU ; Schultz, Nina LU ; Fex, Malin LU and Wennström, Malin LU
- author collaboration
- organization
-
- Clinical Memory Research (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- National Graduate School on Ageing and Health (research group)
- Diabetes - Molecular Metabolism (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- LUDC (Lund University Diabetes Centre)-lup-obsolete (research group)
- publishing date
- 2018-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, amyloid beta, astrocytes, dendritic spines, polyglucosan bodies, α-amylase
- in
- Brain Pathology
- volume
- 28
- issue
- 6
- pages
- 920 - 932
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:29485701
- scopus:85044540839
- ISSN
- 1015-6305
- DOI
- 10.1111/bpa.12597
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: The authors thank Camilla Orbjorn and Samia Hamdan for technical support and Dr Anya Medina Benavente for help with the RT-qPCR measurements. We would also like to acknowledge Dr Simon Moussaud and Dr Henrietta M. Nielsen for the APOE geno-typing, Liliann Frisén for proof reading the manuscript and Arne Brun for scientific input. The work was supported by the Swedish Research Council (Dnr 521-2013-3448). Petrus and Augusta Hedlund Foundation, The Swedish Dementia Foundation, Åke Wiberg Foundation, Alzheimer’s Foundation, Åhlén Foundation, Gun and Bertil Stohnes Foundation and Crafford Foundation. Funding Information: The authors thank Camilla Orbj?rn and Samia Hamdan for technical support and Dr Anya Medina Benavente for help with the RT-qPCR measurements. We would also like to acknowledge Dr Simon Moussaud and Dr Henrietta M. Nielsen for the APOE genotyping, Liliann Fris?n for proof reading the manuscript and Arne Brun for scientific input. The work was supported by the Swedish Research Council (Dnr 521-2013-3448). Petrus and Augusta Hedlund Foundation, The Swedish Dementia Foundation, ?ke Wiberg Foundation, Alzheimer's Foundation, ?hl?n Foundation, Gun and Bertil Stohnes Foundation and Crafford Foundation. Publisher Copyright: © 2018 Lund University. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology Copyright: Copyright 2018 Elsevier B.V., All rights reserved.
- id
- 231f6a3d-04f4-4559-bad4-465d2f6d7102
- date added to LUP
- 2021-08-26 10:16:38
- date last changed
- 2024-11-17 08:08:45
@article{231f6a3d-04f4-4559-bad4-465d2f6d7102, abstract = {{<p>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.</p>}}, author = {{Byman, Elin and Schultz, Nina and Fex, Malin and Wennström, Malin}}, issn = {{1015-6305}}, keywords = {{Alzheimer's disease; amyloid beta; astrocytes; dendritic spines; polyglucosan bodies; α-amylase}}, language = {{eng}}, number = {{6}}, pages = {{920--932}}, publisher = {{Wiley-Blackwell}}, series = {{Brain Pathology}}, title = {{Brain alpha-amylase : a novel energy regulator important in Alzheimer disease?}}, url = {{http://dx.doi.org/10.1111/bpa.12597}}, doi = {{10.1111/bpa.12597}}, volume = {{28}}, year = {{2018}}, }