Distinct brain regional proteome changes in the rTg‐DI rat model of cerebral amyloid angiopathy
| Autor: | Joseph M. Schrader, Feng Xu, William E. Van Nostrand |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Proteomics Pathology medicine.medical_specialty Proteome Amyloid Neutrophils Thalamus Hippocampus Biology Biochemistry Article Cell Degranulation Mass Spectrometry Transforming Growth Factor beta1 Cellular and Molecular Neuroscience medicine Animals Humans Pathology Molecular Neuroinflammation Brain Chemistry Tumor Necrosis Factor-alpha Cerebral infarction Computational Biology Isolated brain medicine.disease Capillaries Rats Cerebral Amyloid Angiopathy Disease Models Animal Neutrophil degranulation Female Cerebral amyloid angiopathy Rats Transgenic |
| Zdroj: | J Neurochem |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | Cerebral amyloid angiopathy (CAA), a prevalent cerebral small vessel disease in the elderly and a common comorbidity of Alzheimer's disease, is characterized by cerebral vascular amyloid accumulation, cerebral infarction, microbleeds, and intracerebral hemorrhages and is a prominent contributor to vascular cognitive impairment and dementia. Here, we investigate proteome changes associated with specific pathological features in several brain regions of rTg-DI rats, a preclinical model of CAA. Whereas varying degrees of microvascular amyloid and associated neuroinflammation are found in several brain regions, the presence of microbleeds and occluded small vessels is largely restricted to the thalamic region of rTg-DI rats, indicating different levels of CAA and associated pathologies occur in distinct brain regions in this model. Here, using SWATHLC-MS/MS, we report specific proteomic analysis of isolated brain regions and employ pathway analysis to correlate regionally specific proteomic changes with uniquely implicated molecular pathways. Pathway analysis suggested common activation of tumor necrosis factor α (TNFα), abnormal nervous system morphology, and neutrophil degranulation in all three regions. Activation of transforming growth factor-β1 (TGF-β1) was common to the hippocampus and thalamus, which share high CAA loads, while the thalamus, which uniquely exhibits thrombotic events, additionally displayed activation of thrombin and aggregation of blood cells. Thus, we present significant and new insight into the cerebral proteome changes found in distinct brain regions with differential CAA-related pathologies of rTg-DI rats and provide new information on potential pathogenic mechanisms associated with these regional disease processes. |
| Databáze: | OpenAIRE |
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