A Potential Role for α -Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)205-217
Antal sidor13
TidskriftJournal of Alzheimer's Disease
Volym68
Utgivningsnummer1
StatusPublished - 2019
PublikationskategoriForskning
Peer review utfördJa