CBBM Lecture by "Intramural periarterial drainage and glymphatic pathways in the brain - Relevance to Alzheimer’s disease."


Roxana O Carare MD, PhD, Professor of Clinical Neuroanatomy, Faculty of Medicine, University of Southampton


will take place on Tuesday, January 14, 2020 from 17:15 to 18:15 hours in CBBM, Ground Floor, Seminar Room B1/B2.

Host: Dr. Markus Krohn
Institute of Pharmacology and Toxicology
University of Lübeck

 

Abstract

Accumulation of the β-amyloid (Aβ) protein in cerebral blood vessels is a hallmark of Alzheimer’s disease. Soluble Aβ from the extracellular spaces of the brain is removed along the basement membranes of capillaries and basement membranes surrounding smooth muscle cells of arteries towards the surface of the brain, as intramural periarterial drainage (IPAD). This process depends on the biochemical integrity of the extracellular matrix and the strength of arterial smooth muscle cells. With ageing, possession of Apolipoprotein E4 (APOE4) genotype, hyperlipidemia, maternal high fat, immune complexes, IPAD fails, resulting in the accumulation of proteins in the walls of cerebral arteries as cerebral amyloid angiopathy. The motive force for IPAD is derived from contractions of vascular smooth muscle cells and targeting their function appears to be a promising therapeutic avenue for Alzheimer’s disease. Convective influx/glymphatic entry of cerebrospinal fluid (CSF) into the cerebral parenchyma is along the glial-pial basement membranes of arteries and tracers from the CSF find their way into the IPAD pathways within half an hour after intracisternal injections. This pathways has implications for drug delivery via intrathecal routes, whereas IPAD has implications for identifying new therapeutic strategies that facilitate the clearance of peptides and fluid from the ageing brain, in Alzheimer’s disease.

 

Biosketch

Roxana Carare qualified in Medicine in Bucharest in 1994. During her basic clinical training, she became fascinated by anatomy and completed her PhD in experimental neuropathology in 2006, in the University of Southampton, UK. She was appointed lecturer in 2001, associate professor in 2014 and professor of clinical neuroanatomy in 2016. The main international recognition for Roxana Carare has come from the interdisciplinary research she leads, investigating the cause of Alzheimer's disease and suggesting therapeutic strategies.Roxana is a member of the MRC Dementia Platform UK Vascular Experimental Medicine committee and the UK government advisory committee for the effects of pollution on the brain. The Carare team has won prestigious awards, including a Dementia Research Leader award from Alzheimer’s Society UK. Roxana has enjoyed teaching anatomy for 20 years, with a passion for neuroanatomy. Roxana is Co-Chair for The International Alliance of Women Alzheimer's Researchers in Alzheimer’s Association and is a member of the Scientific Committee for Alzheimer’s Association.