A Study of Familial Amyloid Polyneuropathy Induced by the TTR Val30Leu Mutation in China.

INTRODUCTION: Familial amyloid polyneuropathy is currently prevalent worldwide as the transthyretin (TTR) Val30Met mutation, and there are other types of mutations. The purpose of this study was to understand the clinical manifestations, electrophysiological characteristics, and outcomes of hormone-related therapy in patients with the TTR Val30Leu mutation in China. METHODS: Clinical data were collected from 9 members of a family with the TTR Val30Leu mutation in China, and blood samples of 7 members of the family were sequenced. The electrophysiological examinations of 4 of them were collected and analysed. RESULTS: A total of 7 people had the TTR gene c.148G>T missense mutation and the TTR protein Val30Leu mutation in this family, and the positive members all had similar symptoms, such as limb paraesthesia and gastrointestinal symptoms. In addition, electrophysiological examination showed abnormal nerve conduction velocity in all 4 patients. CONCLUSIONS: The clinical manifestations of this mutation involve mainly limb sensory or motor disorders or gastrointestinal symptoms or both, and the electrophysiological examination shows neurogenic damage.

Metabolic Reprogramming of Microglia Enhances Proinflammatory Cytokine Release through EphA2/p38 MAPK Pathway in Alzheimer's Disease.

BACKGROUND: The activation of microglia and neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD), but the exact roles of microglia and the underlying mechanisms remain unclear. OBJECTIVE: To clarify how the metabolic reprogramming of microglia induce by amyloid-ß (Aß)1-42 to affect the release of proinflammatory cytokines in AD. METHODS: MTS assay was used to detect the viability of BV2 cells treated with different concentrations of Aß1-42 for different periods of time. The expression levels of proinflammatory cytokines were determined by qRT-PCR and western blot assay in BV2 cells and hippocampus of mice. RNA sequencing was applied to evaluate the gene expression profiles in response to HK2 knockdown in BV2 cells treated with Aß1-42. RESULTS: Low concentrations of Aß1-42 increased the viability of BV2 cells and promoted the release of proinflammatory cytokines, and this process is accompanied by increased glycolysis. Inhibition of glycolysis significantly downregulated the release of proinflammatory cytokines in BV2 cells and hippocampus of mice treated with Aß1-42. The results of RNA sequencing revealed the expression of chemokine ligand 2 (Cxcl2) and ephrin receptor tyrosine kinase A2 (EphA2) were significantly downregulated when knocked down HK2 in BV2 cells. Subsequently, the expression of proinflammatory cytokines was downregulated in BV2 cell after knocking down EphA2. CONCLUSION: This study demonstrated that EphA2/p38 MAPK pathway is involved the release of proinflammatory cytokines in microglia induced by Aß1-42 in AD, which is accompanied by metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis.

Integration-free induced pluripotent stem cell line derived from a 62-years-old male donor with APOE-epsilon4/epsilon4 alleles.

The ε4 allele of the Apolipoprotein E gene (APOE4) continues to be the strongest genetic risk factor associated with sporadic Alzheimer's disease since its discovery compared to the most common ε3 allele. Nevertheless, there is a lack of APOE4-mutant human neuronal models in vitroor in vivo. Hence, we presented an iPSC line of an APOE-ε4/ε4 alleles carrier, a male donor suffering from Alzheimer's disease combined with cerebral infarction. The established iPSC line showed standard characteristics of pluripotency. Collectively, the present study provides a useful resource to reveal the phenotype and explore the mechanism of APOE4 related Alzheimer's disease.