PublicatiesA Potential Role for α-Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation
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 Aβ42 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 Aβ42, with increased pyruvate kinase activity, but unaltered lactate release as downstream events. The fibril Aβ42-induced α-amylase activity was attenuated by β-adrenergic receptor antagonist propranolol.
DISCUSSION: We hypothesize that astrocytes respond to fibril Aβ42 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.
Steun ons werk
De Stichting Vrienden van het Herseninstituut ondersteunt baanbrekend hersenonderzoek. U kunt ons daarbij helpen.Steun ons werk