Roxana Carare is a medically qualified Professor of Clinical Neuroanatomy and experimental neuropathology in the University of Southampton. Having graduated in general medicine in 1994 in Bucharest, Roxana completed her PhD in experimental neuropathology in 2006, in the University of Southampton, UK. The main international recognition for Roxana Carare has come from the neuroanatomy and neuropathology interdisciplinary research she leads, demonstrating the unique lymphatic drainage pathways by which fluid and soluble amyloid are eliminated from the brain along basement membranes within the walls of cerebral capillaries and arteries (Intramural Periarterial Drainage Pathways, IPAD).

ABSTRACT

Title: Using Quasi-Vivo as a system for testing new therapeutic targets in Alzheimer's disease

Author: Abby Keable, Faculty of Medicine, University of Southampton, UK

Maureen Gatherer, Faculty of Medicine, University of Southampton, UK

Roy O Weller, Faculty of Medicine, University of Southampton, UK
Roxana Carare Faculty of Medicine, University of Southampton, UK

Abstract: The failure of intramural periarterial drainage (IPAD) of soluble proteins is a key pathological feature in Alzheimer's disease. The IPAD pathways are within the basement membranes of cerebral capillaries and arteries and therefore they are both small (under 100nm) and inaccessible. Facilitating drainage of fluid and proteins along IPAD pathways is urgent, as no efficient treatment exists for Alzheimer's disease. The QuasiVivo system is optimal for demonstrating the properties of IPAD pathways and showing the effects of drainage of amyloid-beta, mimicking thus the drainage of fluid and amyloid in vivo. We have applied the system to test the hypothesis that the pattern of drainage of soluble amyloid-beta changes in hypoxic conditions that mimic the hypo perfusion that occurs in the elderly brains. Chaperone molecules as well as adrenergic receptor antagonists are excellent candidates to improve IPAD and will be tested in the Quasi Vivo system.

References:

1. Zekonyte J, Sakai K, Nicoll J, Weller RO, Carare RO. Quantification of molecular interactions between apoE, Amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer’s disease. Biophysica et Biochimica Acta, Molecular Basis of Disease 2015
2. Morris AWJ, MacGregor Sharp M, 2. Albargothy NJ, Fernandes R, Hawkes CA, Verma A, Weller RO, Carare RO Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathologica, 2016 May;131(5):725-36.
3. Aldea R…Carare RO, Richardson G. Cerebrovascular smooth muscle cells as the drivers of IPAD. Frontiers in Aging Neuroscience, Jan 2019.

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