Contribution of the BBB in amyloid-b biology in Alzheimer’s disease
© Manu Friederich / Universität Bern

ESR 9 vision / project

Amaia Dominguez-Belloso - Johann Wolfgang Goethe University Frankfurt

ESR 9

Contribution of the BBB in amyloid-b biology in Alzheimer’s disease

Objectives

We show that BACE-1, the proteinase generating neurotoxic β-amyloid (Aβ), is expressed in BBB ECs and becomes up-regulated in an AD mouse model. Hence we hypothesize that BACE-1 at the BBB contributes to AD pathogenesis by Aβ production, leading to BBB dysfunction.
Aim 1: Investigate the factors regulating BACE-1 expression and function at the BBB
Aim 2: Evaluate the role of BACE-1 for APP processing at the BBB in transgenic mouse models
Aim 3: Investigate the impact of BACE-1 at the BBB on drugs targeting BACE-1 in AD

Expected Results

Aim 1: To identify pathways to be involved in BACE-1 regulation at the BBB.
Aim 2: To identify the contribution of endothelial BACE-1 to AD and CAA pathogenesis, and to identify AD-relevant genes regulated in mice deficient in endothelial BACE-1 (BACE-1∆bEC).
Aim 3: To identify the value of endothelial BACE-1 inhibition as a therapeutic target.

Hosting institution

Johann Wolfgang Goethe University Frankfurt, Edinger-Institute Neurology, Germany

Main Supervisor

Stefan Liebner

Early Stage Researcher

Amaia Dominguez-Belloso