PhD Scientific Days 2024

Neurosciences

The role of microglia and inflammation in the pathogenesis of Alzheimer’s Disease

Előadó neve

Dr. Pósfai, Balázs, PhD

Előadó munkahelye

HUN-REN Institute of Experimental Medicine, Budapest, Hungary

Előadó telefonszáma

+36303313010

Előadó e-mail címe

posfai.balazs@koki.hu

Az előadás címe

The role of microglia and inflammation in the pathogenesis of Alzheimer’s Disease

Szerző(k) neve és munkahelye

Balázs Pósfai¹, Sára Vida¹, Krisztina Tóth¹, Nikolett Lénárt¹, Csaba Cserép¹, Zoltán Máté¹, Ferenc Erdélyi¹, Zsolt Lele¹, István Katona¹, Henne Holstege², Olav M. Andersen³, Ádám Dénes¹

1: HUN-REN Institute of Experimental Medicine, Budapest, Hungary
2: Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
3: Department of Biomedicine, Aarhus University, Aarhus, Denmark

Bemutatás módja

Szóbeli

Szekció

Neurosciences

Language of the presentation

English

Preferred session

Neurosciences

Összefoglaló szövege

Introduction: Understanding the mechanisms of neurological diseases is one of the most urgent challenges of medicine. In recent years, our workgroup has contributed to the understanding of the homeostatic and neuroprotective roles of microglia, the brain’s main immune cell under both physiological and pathological conditions. Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is the leading cause of dementia worldwide. In our ongoing experiments, we are exploring the involvement of microglia in the pathogenesis of AD, specifically focusing on microglia-neuron somatic junctions, and on the role of the sortilin-related receptor SORL1, the genetic alteration of which shows a strong correlation with hereditary late-onset AD.
Aims: To assess microglial alterations during the pathogenesis of AD, and study the role of AD-related risk protein SORL1.
Methods: In order to conduct a translational study, we utilize both mouse and human samples. We have collected fixed tissue, native brains and cerebrospinal fluid of triple-transgenic AD-model (PSEN1//App_swe//tauP301L) and control mice, from three different age groups (60-80 days, 220-240 days, 490-520 days) and both sexes. We have also developed a new plasmid and performed in utero electroporation, resulting in the deletion of SORL1 protein in a subpopulation of cortical neurons in transgenic mice. We are processing these samples primarily for cytokine measurements and high-resolution immunofluorescent imaging. We also performed bulk-proteomic and single cell RNA-sequencing measurements on 3 groups of human samples: SORL1-mutation carrying AD patients, age-matched AD and CTRL patients.
Results and conclusions: Our preliminary results show significant alterations of microglia during the aging of AD-model mice, as well as a different dynamic to the expression changes of SORL1-protein. In the human samples, we identified general and cell population-specific SORL1-mutation-related alterations.
Funding: Supported by the ÚNKP-23-4-II-SE-16 New National Excellence Program of the Ministry of Culture and Innovation from the source of the National Research, Development and Innovation Fund and SORLA-FIX JPND.

University

Semmelweis University

Supervisor

Dr. Ádám Dénes

Publication of my abstract

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

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4093

Start

11:30

End

11:40