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Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid \u03b2-protein (A\u03b2) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar A\u03b2 promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of &gt;50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-\u03b21) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-\u03b21 pathway and increased TGF-\u03b21 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-\u03b21 in the disease process.<\/jats:p>","DOI":"10.1177\/26331055241288172","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T12:39:11Z","timestamp":1728391151000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments"],"prefix":"10.1177","volume":"19","author":[{"given":"Joseph M","family":"Schrader","sequence":"first","affiliation":[{"name":"George & Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA"},{"name":"Department of Biomedical & Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, 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