Characterization of the role of Versican in small vessel diseases of the central nervous system.

The brain controls key functions such as perception, memory, and movement. Memory, processed in the dentate gyrus of the hippocampus, is often impaired in pathological conditions like Alzheimer’s disease (AD). Identified by the World Health Organization as a global public health priority, AD is the leading form of dementia, accounting for 80% of cases. The disease is marked by the extracellular accumulation of amyloid-beta (Aβ) plaques and intracellular hyperphosphorylated tau, forming neurofibrillary tangles (NFTs). These abnormalities cause microglial inflammation, neuronal loss, and synaptic disorganization. Additionally, blood-brain barrier (BBB) dysfunction exacerbates neurodegeneration by disrupting exchanges between blood and brain tissue.

This research project was conducted at INSERM U1034, Bordeaux, where we investigated the role of the vascular microenvironment and blood-brain barrier (BBB) in AD, with a particular focus on the  extracellular matrix glycoprotein, Versican (VCAN). A genome-wide association study (GWAS) identified VCAN as a potential therapeutic target and biomarker for cerebral small vessel diseases(cSVD) associated with vascular dementia and AD. VCAN isoforms, which regulate cell migration and proliferation, may play a role in the vascular dysfunction observed in AD. The project aims to investigate how VCAN contributes to BBB alterations and the development of cSVD, which can precede AD. To explore VCAN’s role, zebrafish larvae (n = 50 per group) were used, divided into three groups: larvae injected with anti-VCAN-a morpholinos, a control group with scrambled morpholinos, and an uninjected group. VCAN expression was analyzed using qPCR after RNA extraction and reverse transcription, while Western Blot was employed to characterize VCAN proteins and their modifications. Immunohistochemistry assessed BBB permeability and vascular alterations using specific markers (lectin, fibrinogen). Confocal microscopy fluorescence analyses measured BBB permeability and structural changes. These combined approaches aim to shed light on VCAN’s role in vascular pathologies and its potential as a therapeutic target for AD.

#Alzheimer’s disease #vascular dementia #neurodegeneration #microenvironment #Versican #morpholino

Characterization of the role of Versican in small vessel diseases of the central nervous system.

The brain controls key functions such as perception, memory, and movement. Memory, processed in the dentate gyrus of the hippocampus, is often impaired in pathological conditions like Alzheimer’s disease (AD). Identified by the World Health Organization as a global public health priority, AD is the leading form of dementia, accounting for 80% of cases. The disease is marked by the extracellular accumulation of amyloid-beta (Aβ) plaques and intracellular hyperphosphorylated tau, forming neurofibrillary tangles (NFTs). These abnormalities cause microglial inflammation, neuronal loss, and synaptic disorganization. Additionally, blood-brain barrier (BBB) dysfunction exacerbates neurodegeneration by disrupting exchanges between blood and brain tissue.

This research project was conducted at INSERM U1034, Bordeaux, where we investigated the role of the vascular microenvironment and blood-brain barrier (BBB) in AD, with a particular focus on the  extracellular matrix glycoprotein, Versican (VCAN). A genome-wide association study (GWAS) identified VCAN as a potential therapeutic target and biomarker for cerebral small vessel diseases(cSVD) associated with vascular dementia and AD. VCAN isoforms, which regulate cell migration and proliferation, may play a role in the vascular dysfunction observed in AD. The project aims to investigate how VCAN contributes to BBB alterations and the development of cSVD, which can precede AD. To explore VCAN’s role, zebrafish larvae (n = 50 per group) were used, divided into three groups: larvae injected with anti-VCAN-a morpholinos, a control group with scrambled morpholinos, and an uninjected group. VCAN expression was analyzed using qPCR after RNA extraction and reverse transcription, while Western Blot was employed to characterize VCAN proteins and their modifications. Immunohistochemistry assessed BBB permeability and vascular alterations using specific markers (lectin, fibrinogen). Confocal microscopy fluorescence analyses measured BBB permeability and structural changes. These combined approaches aim to shed light on VCAN’s role in vascular pathologies and its potential as a therapeutic target for AD.

#Alzheimer’s disease #vascular dementia #neurodegeneration #microenvironment #Versican #morpholino

internship supervisor

Virginie DINET