Chakraborty et al., reveal in Brain a new marker for vascular dysfunction during dementia

Alzheimer’s disease is one of the most common forms of neurological disorders affecting the elderly and clinically manifests itself by a gradual decline of cognitive function. Nowadays, it becomes increasingly clear that various vascular risk factors, such as ageing, atherosclerosis, diabetes mellitus, and stroke are known to enhance the risk to develop Alzheimer’s disease. Together, such vascular events may result in a diminished function of the blood-brain barrier, reduced cerebral perfusion and increased hypoxia. To date, markers that reflect ongoing vascular dysfunction in the brain are lacking. Here we provide first evidence that angiopoietin like-4 (ANGPTL4), a hypoxia-induced factor, is produced by reactive astrocytes under pathological conditions and in turn stimulates new vessel formation in a 3D spheroid model. Interestingly, plasma levels of ANGPTL4 are significantly increased in patients with vascular dementia compared to controls with subjective cognitive decline. Overall, our data suggest that ANGPTL4 contributes to pathological vascular remodeling and that detection of ANGPTL4 levels may improve current diagnostics for cerebrovascular dysfunction.

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Article: Ananya Chakraborty, Alwin Kamermans, Bert van het Hof, Kitty Castricum, Ed Aanhane, Jack van Horssen, Victor L Thijssen, Philip Scheltens, Charlotte E Teunissen, Ruud D Fontijn, Wiesje M van der Flier & Helga E de Vries. Angiopoietin like-4 as a novel vascular mediator in capillary cerebral amyloid angiopathy. Brain, awy274.