Immunohistochemical Demonstration of the pGlu79 alpha-Synuclein Fragment in Alzheimer's Disease and Its Tg2576 Mouse Model

Bluhm A, Schrempel S, Schilling S, von Hörsten S, Schulze A, Rossner S, Hartlage-Ruebsamen M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Biomolecules MDPI

Book Volume: 12

Journal Issue: 7

DOI: 10.3390/biom12071006

Abstract

The deposition of beta-amyloid peptides and of alpha-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified alpha-synuclein variant (pGlu79-aSyn)-along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation-in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with beta-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to beta-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27.

Authors with CRIS profile

Stephan von Hörsten Professur für Experimentelle Biomedizin

Involved external institutions

Universität Leipzig DE Germany (DE) Fraunhofer-Institut für Zelltherapie und Immunologie (IZI) DE Germany (DE)

How to cite

APA:

Bluhm, A., Schrempel, S., Schilling, S., von Hörsten, S., Schulze, A., Rossner, S., & Hartlage-Ruebsamen, M. (2022). Immunohistochemical Demonstration of the pGlu79 alpha-Synuclein Fragment in Alzheimer's Disease and Its Tg2576 Mouse Model. Biomolecules, 12(7). https://doi.org/10.3390/biom12071006

MLA:

Bluhm, Alexandra, et al. "Immunohistochemical Demonstration of the pGlu79 alpha-Synuclein Fragment in Alzheimer's Disease and Its Tg2576 Mouse Model." Biomolecules 12.7 (2022).

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