The Role of Neurovascular Compromise, Autoimmune Antibodies and Neuronal Calcium Sensor Proteins During the Onset and Progression of Alzheimer's Disease - Linking the Retina with the Brain

Author(s)

Hao Wu

Date Approved

8-2016

Document Type

Dissertation

Degree Name

PhD in Cell and Molecular Biology

Department

Cell Biology

College

Graduate School of Biomedical Sciences

Funder

New Jersey Health Foundation, Osteopathic Heritage Foundation

First Advisor

Venkataswar Venkataraman, PhD

Committee Member 1

Bernd Spur, PhD

Committee Member 2

Kingsley Yin, PhD

Committee Member 3

Michael D'Andrea, PhD

Committee Member 4

Robert Nagele, PhD

Committee Member 5

John Pastorino, PhD

Subject(s)

Autoimmune Diseases of the Nervous System, Alzheimer Disease, Neuronal Calcium-Sensor Proteins, Neuroinflammatory Diseases, Neurodegenerative Diseases, Retina, Blood-Brain Barrier

Disciplines

Cell Biology | Medical Cell Biology | Medicine and Health Sciences | Nervous System Diseases | Neuroscience and Neurobiology | Pathological Conditions, Signs and Symptoms

Abstract

Alzheimer's disease (AD), the main cause of dementia, is a progressive and irreversible neurodegenerative disease. The pathological hallmarks of the disease include bloodbrain barrier (BBB) breach, neurofibrillary tang les and amyloid plaques. Also, emerging evidence has raised the possibility that instead of a secondary consequence, the neuroinflammation contributes to the development and early progression of AD. However, the mechanism underlying the blood-neural barrier (BNB), chronic inflammation and neuronal degenerative diseases (NDDs) remain to be elucidated.

To explore the role of the chronic inflammation in NDDs and delineate the early steps of these diseases, in vivo drug-induced and transgenic mouse models together with an ex vivo organotypic culture model were generated. Analyses helped establish a temporal sequence of events in both types of models. A chronic compromise of BBB in S100B knockout (S100BKO) mice was reported for the first time. Coincident with the increase in Immunoglobulin G (IgG) - bound cells, autoantibodies targeting brain proteins were detected in the serum. These events were concurrent with neuronal compromise, astrocytic activation and abnormal microglia. Based on the results, a key role for S100B in maintaining the functional integrity of the BNB is proposed.

As a window to the brain, retina was also examined under similar experimental settings. Parallel pathological changes were perceived indicating that the retina, specifically the photoreceptors and Muller cells, was a reliable detector for the associated changes in the brain.

Recommended Citation

Wu, Hao, "The Role of Neurovascular Compromise, Autoimmune Antibodies and Neuronal Calcium Sensor Proteins During the Onset and Progression of Alzheimer's Disease - Linking the Retina with the Brain" (2016). Graduate School of Biomedical Sciences Theses and Dissertations. 56.
https://rdw.rowan.edu/gsbs_etd/56