Venular amyloid accumulation in transgenic Fischer 344 Alzheimer's disease rats.

Strong evidence demonstrates a significant association between cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). For this reason, interest in understanding the underlying vascular pathologies that contribute to AD remain. CAA 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 (Aß) sequence suggest morphological differences between arteriolar and venular amyloid. Mass spectrometric analyses of isolated cortical parenchymal plaques, arteriolar and venular amyloid demonstrated presence of Aß 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, significant arteriolar amyloid accumulates relative to venular amyloid deposition in AD progression. Overall, understanding venular and arteriolar amyloid pathology provides insight into the complex connection between CAA and AD.

The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15.

Clathrin-mediated endocytosis is a multistep process which requires interaction between a number of conserved proteins. We have cloned two mammalian genes which code for a number of endocytic adaptor proteins. Two of these proteins, termed Ese1 and Ese2, contain two N-terminal EH domains, a central coiled-coil domain and five C-terminal SH3 domains. Ese1 is constitutively associated with Eps15 proteins to form a complex with at least 14 protein-protein interaction surfaces. Yeast two-hybrid assays have revealed that Ese1 EH and SH3 domains bind epsin family proteins and dynamin, respectively. Overexpression of Ese1 is sufficient to block clathrin-mediated endocytosis in cultured cells, presumably through disruption of higher order protein complexes, which are assembled on the endogenous Ese1-Eps15 scaffold. The Ese1-Eps15 scaffold therefore links dynamin, epsin and other endocytic pathway components.