Neuronal α-amylase is important for neuronal activity and glycogenolysis and reduces in presence of amyloid beta pathology
Byman, Elin LU ; Martinsson, Isak LU ; Haukedal, Henriette ; Gouras, Gunnar LU
; Freude, Kristine K
and Wennström, Malin
LU
(2021)
In Aging Cell
20(8).
- Abstract
Recent studies indicate a crucial role for neuronal glycogen storage and degradation in memory formation. We have previously identified alpha-amylase (α-amylase), a glycogen degradation enzyme, located within synaptic-like structures in CA1 pyramidal neurons and shown that individuals with a high copy number variation of α-amylase perform better on the episodic memory test. We reported that neuronal α-amylase was absent in patients with Alzheimer's disease (AD) and that this loss corresponded to increased AD pathology. In the current study, we verified these findings in a larger patient cohort and determined a similar reduction in α-amylase immunoreactivity in the molecular layer of hippocampus in AD patients. Next, we demonstrated... (More)
Recent studies indicate a crucial role for neuronal glycogen storage and degradation in memory formation. We have previously identified alpha-amylase (α-amylase), a glycogen degradation enzyme, located within synaptic-like structures in CA1 pyramidal neurons and shown that individuals with a high copy number variation of α-amylase perform better on the episodic memory test. We reported that neuronal α-amylase was absent in patients with Alzheimer's disease (AD) and that this loss corresponded to increased AD pathology. In the current study, we verified these findings in a larger patient cohort and determined a similar reduction in α-amylase immunoreactivity in the molecular layer of hippocampus in AD patients. Next, we demonstrated reduced α-amylase concentrations in oligomer amyloid beta 42 (Aβ42 ) stimulated SH-SY5Y cells and neurons derived from human-induced pluripotent stem cells (hiPSC) with PSEN1 mutation. Reduction of α-amylase production and activity, induced by siRNA and α-amylase inhibitor Tendamistat, respectively, was further shown to enhance glycogen load in SH-SY5Y cells. Both oligomer Aβ42 stimulated SH-SY5Y cells and hiPSC neurons with PSEN1 mutation showed, however, reduced load of glycogen. Finally, we demonstrate the presence of α-amylase within synapses of isolated primary neurons and show that inhibition of α-amylase activity with Tendamistat alters neuronal activity measured by calcium imaging. In view of these findings, we hypothesize that α-amylase has a glycogen degrading function within synapses, potentially important in memory formation. Hence, a loss of α-amylase, which can be induced by Aβ pathology, may in part underlie the disrupted memory formation seen in AD patients.
(Less)
- author
- Byman, Elin
LU
; Martinsson, Isak
LU
; Haukedal, Henriette
; Gouras, Gunnar
LU
; Freude, Kristine K
and Wennström, Malin
LU
- author collaboration
- organization
- publishing date
- 2021-07-14
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Aging Cell
- volume
- 20
- issue
- 8
- article number
- e13433
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:34261192
- scopus:85111804153
- ISSN
- 1474-9726
- DOI
- 10.1111/acel.13433
- language
- English
- LU publication?
- yes
- id
- 8fe3d810-00cc-4ccb-8da4-de2325cc44ba
- date added to LUP
- 2021-07-23 12:55:16
- date last changed
- 2024-06-15 13:40:56
@article{8fe3d810-00cc-4ccb-8da4-de2325cc44ba,
abstract = {{<p>Recent studies indicate a crucial role for neuronal glycogen storage and degradation in memory formation. We have previously identified alpha-amylase (α-amylase), a glycogen degradation enzyme, located within synaptic-like structures in CA1 pyramidal neurons and shown that individuals with a high copy number variation of α-amylase perform better on the episodic memory test. We reported that neuronal α-amylase was absent in patients with Alzheimer's disease (AD) and that this loss corresponded to increased AD pathology. In the current study, we verified these findings in a larger patient cohort and determined a similar reduction in α-amylase immunoreactivity in the molecular layer of hippocampus in AD patients. Next, we demonstrated reduced α-amylase concentrations in oligomer amyloid beta 42 (Aβ42 ) stimulated SH-SY5Y cells and neurons derived from human-induced pluripotent stem cells (hiPSC) with PSEN1 mutation. Reduction of α-amylase production and activity, induced by siRNA and α-amylase inhibitor Tendamistat, respectively, was further shown to enhance glycogen load in SH-SY5Y cells. Both oligomer Aβ42 stimulated SH-SY5Y cells and hiPSC neurons with PSEN1 mutation showed, however, reduced load of glycogen. Finally, we demonstrate the presence of α-amylase within synapses of isolated primary neurons and show that inhibition of α-amylase activity with Tendamistat alters neuronal activity measured by calcium imaging. In view of these findings, we hypothesize that α-amylase has a glycogen degrading function within synapses, potentially important in memory formation. Hence, a loss of α-amylase, which can be induced by Aβ pathology, may in part underlie the disrupted memory formation seen in AD patients.</p>}},
author = {{Byman, Elin and Martinsson, Isak and Haukedal, Henriette and Gouras, Gunnar and Freude, Kristine K and Wennström, Malin}},
issn = {{1474-9726}},
language = {{eng}},
month = {{07}},
number = {{8}},
publisher = {{Wiley-Blackwell}},
series = {{Aging Cell}},
title = {{Neuronal α-amylase is important for neuronal activity and glycogenolysis and reduces in presence of amyloid beta pathology}},
url = {{http://dx.doi.org/10.1111/acel.13433}},
doi = {{10.1111/acel.13433}},
volume = {{20}},
year = {{2021}},
}