Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients. Issue 11 (November 2022)

• Record Type: Journal Article
• Authors: Suzuki, Masayoshi; Tezuka, Kenta; Handa, Takumi; Sato, Risa; Takeuchi, Hina; Takao, Masaki; Tano, Mitsutoshi; Uchida, Yasuo
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 42:Issue 11(2022)
• Page Start: 2134
• Page End: 2150
• Publication Date: 2022-11
• Subjects: Ribosome -- protein processing -- N-glycosylation -- Alzheimer's disease -- blood-brain barrier; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X221111602
• Languages: English
• ISSNs: 0271-678X

Abstract

The cerebrovascular-specific molecular mechanism in Alzheimer's disease (AD) was investigated by employing comprehensive and accurate quantitative proteomics. Highly purified brain capillaries were isolated from cerebral gray and white matter of four AD and three control donors, and examined by SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Of the 29 ribosomal proteins that were quantified, 28 (RPLP0, RPL4, RPL6, RPL7A, RPL8, RPL10A, RPL11, RPL12, RPL14, RPL15, RPL18, RPL23, RPL27, RPL27A, RPL31, RPL35A, RPS2, RPS3, RPS3A, RPS4X, RPS7, RPS8, RPS14, RPS16, RPS20, RPS24, RPS25, and RPSA) were significantly upregulated in AD patients. This upregulation of ribosomal protein expression occurred only in brain capillaries and not in brain parenchyma. The protein expression of protein processing and N-glycosylation-related proteins in the endoplasmic reticulum (DDOST, STT3A, MOGS, GANAB, RPN1, RPN2, SEC61B, UGGT1, LMAN2, and SSR4) were also upregulated in AD brain capillaries and was correlated with the expression of ribosomal proteins. The findings reported herein indicate that the ribosome complex, the subsequent protein processing and N-glycosylation-related processes are significantly and specifically upregulated in the brain capillaries of AD patients.