Venular amyloid accumulation subsequent to cerebral amyloid angiopathy in transgenic Fischer 344 Alzheimer’s disease rats

Abstract Strong evidence demonstrates a significant association between cerebral amyloid angiopathy and Alzheimer’s disease (AD). For this reason, interest in understanding the underlying vascular pathologies that contribute to AD remain. Cerebral amyloid angiopathy research has primarily focused on arterioles and capillaries, overlooking the draining venules. Therefore, this study sought to examine venular amyloid pathology and its relationship to arteriolar amyloidosis throughout AD progression in the TgF344-AD rat model. Antibodies targeting the amyloid-beta peptide (Ab) sequence suggest morphological differences between arteriolar and venular amyloid. Mass spectrometric analyses of isolated cortical parenchymal plaques, arteriolar and venular amyloid demonstrated presence of Ab in all three samples, as well as proteins known to be associated with AD. Histopathological analysis indicates a significant age effect for both arteriolar and venular amyloid accumulation, with accumulation initiated in the somatosensory cortex followed by the motor and cingulate cortex. Lastly, arteriolar amyloid accumulates prior to venular amyloid deposition and at a faster rate earlier in AD progression. Overall, understanding venular and arteriolar amyloid pathology provides insight into the complex connection between cerebral amyloid angiopathy and AD.