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Vascular Changes in Iowa‐Type Hereditary Cerebral Amyloid Angiopathy

Abstract: Vascular dysfunction due to cerebral amyloid angiopathy (CAA) may contribute to cognitive impairment. The Iowa D694N amyloid precursor protein mutation, a recently identified cause of hereditary CAA with dementia, offers an opportunity to explore the anatomic basis of CAA‐related vascular dysfunction. Examination by immunolabeling and confocal microscopy demonstrated extensive loss of smooth muscle cells in affected segments as well as a perivascular inflammatory reaction of astrocytes and microglia. On 3‐D reconstruction, vessels appeared tortuous with twiglike projections that may represent areas of vascular degeneration. The observed changes in the Iowa brain suggest pathophysiologic mechanisms for vascular dysfunction in CAA and possible approaches to treatment of CAA‐related cognitive impairment.