A Potential Role for α -Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation
Byman, Elin LU ; Schultz, Nina LU ; Blom, Anna M. LU
and Wennström, Malin
LU
(2019)
In Journal of Alzheimer's Disease
68(1).
p.205-217
- Abstract
Background: Astrocytes produce and store the energy reserve glycogen. However, abnormal large glycogen units accumulate if the production or degradation of glycogen is disturbed, a finding often seen in patients with Alzheimer's disease (AD). We have shown increased activity of glycogen degrading α-amylase in AD patients and α-amylase positive glial cells adjacent to AD characteristic amyloid-β (Aβ) plaques. Objectives: Investigate the role of α-amylase in astrocytic glycogenolysis in presence of Aβ. Methods: Presence of α-amylase and large glycogen units in postmortem entorhinal cortex from AD patients and non-demented controls were analyzed by immunohistological stainings. Impact of different Aβ 42 aggregation forms on enzymatic... (More)
Background: Astrocytes produce and store the energy reserve glycogen. However, abnormal large glycogen units accumulate if the production or degradation of glycogen is disturbed, a finding often seen in patients with Alzheimer's disease (AD). We have shown increased activity of glycogen degrading α-amylase in AD patients and α-amylase positive glial cells adjacent to AD characteristic amyloid-β (Aβ) plaques. Objectives: Investigate the role of α-amylase in astrocytic glycogenolysis in presence of Aβ. Methods: Presence of α-amylase and large glycogen units in postmortem entorhinal cortex from AD patients and non-demented controls were analyzed by immunohistological stainings. Impact of different Aβ 42 aggregation forms on enzymatic activity (α-amylase, pyruvate kinase, and lactate dehydrogenase), lactate secretion, and accumulation of large glycogen units in cultured astrocytes were analyzed by activity assays, ELISA, and immunocytochemistry, respectively. Results: AD patients showed increased number of α-amylase positive glial cells. The glial cells co-expressed the astrocytic marker glial fibrillary acidic protein, displayed hypertrophic features, and increased amount of large glycogen units. We further found increased load of large glycogen units, α-amylase immunoreactivity and α-amylase activity in cultured astrocytes stimulated with fibril Aβ 42, with increased pyruvate kinase activity, but unaltered lactate release as downstream events. The fibril Aβ 42 -induced α-amylase activity was attenuated by β-adrenergic receptor antagonist propranolol. Discussion: We hypothesize that astrocytes respond to fibril Aβ 42 in Aβ plaques by increasing their α-amylase production to either liberate energy or regulate functions needed in reactive processes. These findings indicate α-amylase as an important actor involved in AD associated neuroinflammation.
(Less)
- author
- Byman, Elin
LU
; Schultz, Nina
LU
; Blom, Anna M.
LU
and Wennström, Malin
LU
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, amyloid-β, astrocytes, glycogenolysis, α -amylase
- in
- Journal of Alzheimer's Disease
- volume
- 68
- issue
- 1
- pages
- 13 pages
- publisher
- IOS Press
- external identifiers
-
- scopus:85062822333
- pmid:30775997
- ISSN
- 1387-2877
- DOI
- 10.3233/JAD-180997
- language
- English
- LU publication?
- yes
- id
- 2ea3bb40-73a8-4458-862c-c5f5dc552dab
- date added to LUP
- 2019-03-21 13:27:41
- date last changed
- 2024-06-11 07:03:07
@article{2ea3bb40-73a8-4458-862c-c5f5dc552dab,
abstract = {{<p>Background: Astrocytes produce and store the energy reserve glycogen. However, abnormal large glycogen units accumulate if the production or degradation of glycogen is disturbed, a finding often seen in patients with Alzheimer's disease (AD). We have shown increased activity of glycogen degrading α-amylase in AD patients and α-amylase positive glial cells adjacent to AD characteristic amyloid-β (Aβ) plaques. Objectives: Investigate the role of α-amylase in astrocytic glycogenolysis in presence of Aβ. Methods: Presence of α-amylase and large glycogen units in postmortem entorhinal cortex from AD patients and non-demented controls were analyzed by immunohistological stainings. Impact of different Aβ 42 aggregation forms on enzymatic activity (α-amylase, pyruvate kinase, and lactate dehydrogenase), lactate secretion, and accumulation of large glycogen units in cultured astrocytes were analyzed by activity assays, ELISA, and immunocytochemistry, respectively. Results: AD patients showed increased number of α-amylase positive glial cells. The glial cells co-expressed the astrocytic marker glial fibrillary acidic protein, displayed hypertrophic features, and increased amount of large glycogen units. We further found increased load of large glycogen units, α-amylase immunoreactivity and α-amylase activity in cultured astrocytes stimulated with fibril Aβ 42, with increased pyruvate kinase activity, but unaltered lactate release as downstream events. The fibril Aβ 42 -induced α-amylase activity was attenuated by β-adrenergic receptor antagonist propranolol. Discussion: We hypothesize that astrocytes respond to fibril Aβ 42 in Aβ plaques by increasing their α-amylase production to either liberate energy or regulate functions needed in reactive processes. These findings indicate α-amylase as an important actor involved in AD associated neuroinflammation.</p>}},
author = {{Byman, Elin and Schultz, Nina and Blom, Anna M. and Wennström, Malin}},
issn = {{1387-2877}},
keywords = {{Alzheimer's disease; amyloid-β; astrocytes; glycogenolysis; α -amylase}},
language = {{eng}},
number = {{1}},
pages = {{205--217}},
publisher = {{IOS Press}},
series = {{Journal of Alzheimer's Disease}},
title = {{A Potential Role for α -Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation}},
url = {{http://dx.doi.org/10.3233/JAD-180997}},
doi = {{10.3233/JAD-180997}},
volume = {{68}},
year = {{2019}},
}