Vascular injury accelerates the onset of ALS neurodegeneration: evidence from mouse models and patients.

Speaker: Sebastian Lewandowski PhD (Karolinska Institute, MBB, Stockholm, Sweden)

Talk: Vascular injury accelerates the onset of ALS neurodegeneration: evidence from mouse models and patients.

Time: 30 June 2017, 9 am

Venue: Intercollegiate Faculty of Biotechnology, Abrahama 58

Efficient delivery of oxygen and nutrients is essential for correct brain function. Our studies focus on the mechanisms of vascular injury to explain dysfunction of the blood-brain barrier and decreased cerebral blood flow in patients with amyotrophic lateral sclerosis (ALS). We found that presymptomatic activation of the PDGFC pathway leads to dysfunction of the blood-brain barrier in ALS mouse models and is correlated with younger age at disease onset in mouse models and patients. Vascular injury also leads to dysfunction of the vascular basement membrane where perivascular astrocytes detach from cerebral blood vessels and increase expression of specific extracellular matrix proteins. We found that the increase of vascular basement membrane proteins in plasma of ALS patients is correlated with decreased levels of glucose brain uptake and younger age at disease onset. In summary our findings show that cerebral vessel injury can be a risk factor for young onset of ALS neurodegeneration.