Jasmin Hefendehl: Ischemic Stroke Reveals a Protective Microglial Response in Alzheimer’s Pathology
Jasmin Hefendehl, Professor at the Institute for Cell Biology an Neuroscience at Goethe University Frankfurt, shared on LinkedIn about a recent article she and her colleagues co-authored, published in Journal of Neuroinflammation, adding:
”Thrilled to share our new paper featuring my favorite cell type – Microglia, just published in the Journal of Neuroinflammation: ‘Ischemic injury triggers a protective microglial phenotype in models of Aβ pathology’.
Here’s what we found: when ischemic stroke occurs in the context of Alzheimer’s pathology, instead of simply amplifying the canonical disease-associated microglial response, the peri-infarct microenvironment triggers something qualitatively different.
Microglia upregulate ApoE, ramp up lipid handling, and compact amyloid-beta plaques into dense, relatively inert structures with less neurotoxic halo and fewer dystrophic neurites.
These peri-infarct plaques are strikingly similar to those seen in cognitively resilient Alzheimer’s patients.
Using scRNA-seq, spatial transcriptomics, and confocal Raman microscopy, we show that the microglial compartment retains plasticity, and the right stimulus can unlock a functionally superior response to Aβ.
ApoE emerged as the single gene consistently upregulated across every relevant microglial cluster and every peri-infarct plaque-associated spatial spot.
These findings open the door to pharmacologically recapitulating this protective phenotype.
Huge congratulations to co-first authors Dr. Michael Candlish and Jan Hofmann, and to our whole team of collaborators.”
Title: Ischemic injury triggers a protective microglial phenotype in models of Aβ pathology
Authors: Michael Candlish, Jan Hofmann, Desirée Brösamle, Annika Haessler, Murphy DeMeglio, Angelos Skodras, Georgi Tushev, Eloah S. De Biasi, Stefan Günther, René Wiegandt, Heidi Theis, Elena De Domenico, Nina Sofia Hermann, Peter Breunig, Christina Sauerland, K. Peter R. Nilsson, Marc D. Beyer, Mario Looso, Maike Windbergs, Sigrun Roeber, Jochen Herms, Jonas J. Neher, Andreas G. Chiocchetti, Jasmin K. Hefendehl
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