Joseph Schrader, PhD
Awards
Advance-CTR Pilot Projects Program (Cycle 7)
"Specificity of Brain Protein Biomarkers in Cerebral Amyloid Angiopathy"
According to the 2020 Rhode Island Health Aging Data Report, there has been a 23% increase in Rhode Islanders aged > 60 years since 2016, and Rhode Island has the third highest percentage of people aged > 85 years in the United States. CAA is highly prevalent in the aged population. Further, as reported by the Alzheimer’s Association, 24,000 Rhode Islanders over the age of 65 suffer from AD in which CAA is a significant pathological component that contributes to cognitive impairment and dementia. Thus, CAA poses a critical health burden in the state of Rhode Island.
Cerebral amyloid angiopathy (CAA) is a prevalent cerebral small vessel disease (CSVD), occurring in > 50% of people over the age of 80 years, and is a comorbidity in > 80% of Alzheimer’s Disease (AD) cases. Arising from fibrillar amyloid β (Aβ) deposition in cortical arteries and arterioles and brain capillaries, CAA is marked clinically by cerebral infarction, microbleeds and intracerebral hemorrhages, and is a prominent contributor to vascular cognitive impairment and dementia (VCID).
Despite obvious clinical relevance, the underlying mechanisms linking vascular Aβ deposition to the development of severe vasculopathies are poorly understood, and therapeutic strategies are extremely limited. While characteristic clinical presentations are evident via neuroimaging in later stages of disease, there are no currently validated early stage molecular biomarkers for CAA. Preclinical experiments utilizing protein mass spectrometry can identify protein signatures and potential novel biomarkers of disease, that, following validation in human patient samples, can be further developed as clinical diagnostic tests.
Dr. Schrader's study will investigate whether differentially expressed proteins in a preclinical rat model of CAA are unique when compared to those in a non-amyloidal model of CSVD (SHR-SP hypertensive rats) or a model of parenchymal, rather than vascular, amyloid pathology (AD rats). Brain regions from archival collected tissue samples from CAA, SHR-SP and AD rats will be used for proteomic analysis via mass spectrometry. Differentially expressed proteins identified as unique to the CAA model will then be assessed in emergent stages of the disease. Isolated brain regions from archival tissue of CAA rats in initial disease stages, prior to emergence of severe pathologies, will also undergo proteomic analysis. Altered proteins identified as unique to CAA when compared with other VCID models that are also differentially expressed in early disease stages will be selected as potential diagnostic biomarkers for CAA.