Project description:Our study aimed to investigate the impact of germlineTrem2knockout in Tg-SwDI mice, a transgenic mouse model of cerebral amyloid angiopathy and Alzheimer's disease.
Project description:RNA transcriptome analysis results were utilized to assess the shared gene expression between patients with cerebral amyloid angiopathy (CAA) and those with insomnia.
Project description:Quantitative label-free proteomics study comparing brain samples from subjects with Cerebral amyloid angiopathy, Alzheimer desease and healthy Control groups.
Project description:Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer’s disease in which amyloid-β (Aβ) deposits in cerebral and leptomeningeal vessel walls, predisposing to micro- and macro-hemorrhage. The vessel wall has distinct proteins and heparan sulfate (HS), linear polysaccharides that bind Aβ and promote fibril formation in vitro. Yet how vascular proteins and HS jointly associate with Aβ is unknown. Here we conducted a multi-omics study to systematically characterize the proteins as well as the HS abundance, sulfation level, and disaccharide composition of leptomeninges from 23 moderate to severe CAA cases and controls. We then analyzed the associations between Aβ and other proteins, HS, and apolipoprotein E (ApoE) genotype. We found an increase in a minor HS disaccharide, unsubstituted glucosamine, as well as 6-O sulfated disaccharides, and Aβ40 levels positively correlated with unsubstituted glucosamine. Our findings of vascular HS and protein alterations specific to CAA-affected leptomeningeal vessels provide molecular insight into the extracellular remodeling co-occurring with Aβ deposits, and provide a basis for ante-mortem diagnostic assay development and therapeutic strategies to impede Aβ - HS interaction.
Project description:HCHWA-D is an early onset hereditary form of Cerebral Amyloid Angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the Amyloid Precursor Protein (APP). Post-mortem brain tissue (9 patients and 9 age-related controls; frontal and occipital cortex) was used for next generation sequencing of RNA (RNA-Seq with ribosomal RNA depletion).
Project description:This project utilized UPLC TripleTOF MS/MS and data independent acquisition (DIA), and spectral analysis in Spectronaut (Biognosys) to study brain regional proteomic changes in a cerebral amyloid angiopathy pre-clinical model, rTg-DI. Results revealed similar and regionally distinct differentially expressed proteins in rTg-DI rats.
Project description:This project utilized a timsTOF Pro instrument (Bruker) and applied a data independent acquisition (DIA) method, followed by spectral analysis in PaSER (Bruker) to study proteomic changes in the cerebrospinal fluid of sporadic cerebral amyloid angiopathy patients. Results revealed distinct differentially expressed proteins in sCAA patients.
Project description:This project utilized a timsTOF Pro instrument (Bruker) and applied a data independent acquisition (DIA) method, followed by spectral analysis in PaSER (Bruker) to study proteomic changes in the cerebrospinal fluid of a cerebral amyloid angiopathy pre-clinical model, rTg-DI. Results revealed distinct differentially expressed proteins in rTg-DI rats.
