PhD Scientific Days 2026

Neurosciences

Microglial and Intercellular Signaling Alterations in SORL1-Associated and Sporadic Alzheimer’s Disease

Előadó neve

Dr. Pósfai, Balázs, PhD

Előadó munkahelye

HUN-REN Institute of Experimental Medicine

Előadó telefonszáma

+36303313010

Előadó e-mail címe

posfai.balazs@koki.hu

Az előadás címe

Microglial and Intercellular Signaling Alterations in SORL1-Associated and Sporadic Alzheimer’s Disease

Szerző(k) neve és munkahelye

Balázs Pósfai¹, Sára Vida¹, Krisztina Tóth¹, Ádám Dénes¹

1: HUN-REN Institute of Experimental Medicine

Bemutatás módja

Szóbeli

Szekció

Neurosciences

Language of the presentation

English

Preferred session

Neurosciences

Összefoglaló szövege

Introduction: Microglial homeostasis and efficient intercellular communication are essential for maintaining central nervous system integrity, but both are disrupted in neurodegenerative disorders. In Alzheimer’s disease (AD), the precise pathogenic mechanisms and the associated cell-type-specific alterations remain incompletely understood. We analyzed transcriptomic profiles and intercellular signaling pathways in brain tissue from patients carrying a familial AD-causing protein-truncating variant (PTV) in SORL1, as well as from sporadic AD patients and controls.
Aims: To identify condition-specific microglial subtypes and map alterations in intercellular communication in AD with different genetic backgrounds.
Methods: Single-cell RNA sequencing was performed on temporal cortex samples from 7 individuals (2 SORL1 PTV, 2 sporadic AD, 3 controls). Expression of more than 17,000 genes was examined in 33,824 cells. Data were analyzed in R using the Seurat package, while ligand-receptor interactions were assessed with LIANA.
Results: Distinct transcriptomic alterations were observed across AD groups with different genetic backgrounds, indicating mitochondrial and signaling deficits even in microglia retaining homeostatic profiles. LIANA analysis revealed that intercellular communication is markedly impaired in SORL1 PTV cases, with interactions involving microglia, oligodendrocytes, and oligodendrocyte precursor cells (OPCs) being particularly affected. In microglia, 24 signaling pathways were weakened compared with controls and 13 compared with sporadic AD. Protective microglial signals, such as GRN, were reduced, whereas pro-inflammatory IL-16-mediated microglial signaling was enhanced in PTV cases.
Conclusion: AD cases with different genetic backgrounds show distinct patterns of intercellular communication and alternative trajectories of microglial transformation. Early-onset SORL1-related AD is characterized by less prominent vascular involvement but marked disruption of signaling among microglia, oligodendrocytes, and OPCs. These findings may contribute to a better understanding of pathological mechanisms in AD.
Funding: EKÖP-2025-433, János Bolyai Research Scholarship

University

Semmelweis University

Supervisor

Ádám Dénes

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8930

Start

15:00

End

15:10