Effect of amyloid‐β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)‐3β. (June 2015)

• Record Type: Journal Article
• Authors: Amin, Jay; Paquet, Claire; Baker, Alex; Asuni, Ayodeji A.; Love, Seth; Holmes, Clive; Hugon, Jacques; Nicoll, James A. R.; Boche, Delphine
• Is Part Of: Neuropathology & applied neurobiology. Volume 41:Number 4(2015)
• Page Start: 445
• Page End: 457
• Publication Date: 2015-06
• Subjects: Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12205
• Languages: English
• ISSNs: 0305-1846

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="nan12205-sec-0001" sec-type="section"> <title>Aims</title> <p>Active amyloid‐β (Aβ) immunotherapy in Alzheimer's disease (AD) induces removal of Aβ and phosphorylated tau (ptau). Glycogen synthase kinase (GSK)‐3β is a kinase, responsible for phosphorylation of tau, activation of which can be induced by phosphorylated double‐stranded RNA‐dependent protein kinase (pPKR). Using a <italic>post‐mortem</italic> cohort of immunized AD cases, we investigated the effect of Aβ immunization on GSK‐3β expression and pPKR.</p> </sec> <sec id="nan12205-sec-0002" sec-type="section"> <title>Methods</title> <p>We immunostained 11 immunized AD cases and 28 unimmunized AD cases for active, inactive and total GSK‐3β, and for pPKR. Quantification of protein load was performed in the hippocampal region including CA1, subiculum and entorhinal cortex.</p> </sec> <sec id="nan12205-sec-0003" sec-type="section"> <title>Results</title> <p>All three areas showed a significant decrease in the three forms of GSK‐3β (<italic>P</italic> < 0.05) and a nonsignificant trend towards lower pPKR load in the immunized AD cases compared with the unimmunized AD cases.</p> </sec> <sec id="nan12205-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The lower GSK‐3β expression generated by Aβ immunotherapy shows evidence of a modification of the signalling pathway induced by GSK‐3β leading to the overall reduction of tau, supporting the contention that in humans, GSK‐3β unifies Aβ and tau‐related neuropathology.</p> </sec> </abstract>