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ePoster
PROTEIN-TRUNCATING VARIANTS OF SORL1 INITIATE SPECIFIC PROTEOMIC AND TRANSCRIPTOMIC ALTERATIONS IN ALZHEIMER’S DISEASE
Balázs Pósfaiand 5 co-authors
HUN-REN Institute of Experimental Medicine
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS05-09AM-190
Presentation
Date TBA
Board: PS05-09AM-190
Event Information
Poster Board
PS05-09AM-190
Poster
View posterAbstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Understanding its mechanisms is one of the most urgent challenges of medicine. Rare protein-truncating variants (PTV) of the sortilin-related receptor SORL1 lead to hereditary early-onset AD. In this study, we identify common characteristics and alterations between PTV-carriers and sporadic AD patients through a multiomic approach on postmortem samples.
We performed bulk proteomic measurements on human temporal cortex samples and CSF, followed by single-cell sequencing and spatial transcriptomic experiments. The study involves tissue from PTV carriers, age and Braak stage-matched AD and control patients.
Our experiments revealed region-specific differences between SORL1-dependent and sporadic AD, with extensively more changes in the temporal cortex grey matter, than in the white matter or CSF. Major differences between PTV and AD samples include pathways linked to protein synthesis and folding, as well as mitochondrial function and immune response. Spatial transcriptomic measurements revealed further layer-specific alterations in the transcriptome. Our results highlight the prominent role of microglia and exacerbated neuroinflammatory processes in PTV cases, providing an explanation for the enhanced disease progression in SORL1-mutation carrying patients. Understanding common characteristics and alterations between PTV-carriers and sporadic AD patients may shed light to some novel inflammatory mechanisms underlying the pathogenesis of AD.
We performed bulk proteomic measurements on human temporal cortex samples and CSF, followed by single-cell sequencing and spatial transcriptomic experiments. The study involves tissue from PTV carriers, age and Braak stage-matched AD and control patients.
Our experiments revealed region-specific differences between SORL1-dependent and sporadic AD, with extensively more changes in the temporal cortex grey matter, than in the white matter or CSF. Major differences between PTV and AD samples include pathways linked to protein synthesis and folding, as well as mitochondrial function and immune response. Spatial transcriptomic measurements revealed further layer-specific alterations in the transcriptome. Our results highlight the prominent role of microglia and exacerbated neuroinflammatory processes in PTV cases, providing an explanation for the enhanced disease progression in SORL1-mutation carrying patients. Understanding common characteristics and alterations between PTV-carriers and sporadic AD patients may shed light to some novel inflammatory mechanisms underlying the pathogenesis of AD.
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