Evidence that glial cells attenuate G47R transthyretin accumulation in the central nervous system

This study aimed to clarify the reason why amyloid transthyretin (ATTR) rarely accumulates in the CNS. We pathologically analyzed the relationship between amyloid deposition with basement membranes or glial cells in a rare case of ATTR leptomeningeal amyloidosis. In addition, we compared the cytotoxicity of ATTR G47R, the amyloidosis‐causing mutation in the case studied (n = 1), and Aβ in brains from patients with cerebral amyloid angiopathy (n = 6). In the subarachnoid space of the ATTR G47R case, most amyloids accumulated at the components of basement membranes. On the CNS surface, ATTR accumulations were retained by astrocytic end feet. In areas where glial end feet enveloped ATTR, ubiquitination and micro‐vacuolation of ATTR was evident. The colocalization of GFAP and ubiquitin was also evident. The accumulation of ATTR G47R in the CNS was negatively correlated with the prevalence of astrocytes. Quantitatively, amyloid deposits along the vessels were mostly partial in cerebral Aβ angiopathy cases and nearly complete along the basement membrane in the ATTR G47R case. The vascular expressions of type IV collagen and smooth muscle actin were severely reduced in areas with ATTR G47R deposition, but not in areas with Aβ deposition. The vascular protein level recovered in the ATTR G47R case when vessels entered into areas of parenchyma that were rich in astrocytes. In addition, the strong interactions between the transthyretin variant and basement membranes may h...

Source: Neuropathology - August 1, 2017 Category: Neurology Authors: Hisae Sumi ‐Akamaru, Masaki Eto, Amane Yamauchi, Takuya Uehara, Keita Kakuda, Konen Obayashi, Shinsuke Kato, Takashi Naka, Hideki Mochizuki Tags: Original Article Source Type: research