Lack of association between LGMN and Alzheimer’s disease in the Southern Han Chinese population

Abstract

Recently, functional studies have demonstrated that legumain (LGMN) cleaves both amyloid β-protein precursor and tau, promoting senile plaques and formation of neurofibrillary tangles, which may play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the genetic role of LGMN in AD has not been clearly elucidated. Here, we used Sanger sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effects of variants in the LGMN gene as potential susceptibility factors for AD, in a cohort comprising 676 AD cases and 365 elderly controls from the Han population of South China. In single-variant association analysis, none of the common variants in LGMN were statistically significant. In gene-based analysis, the LGMN gene also showed no association with AD. The results of our replication study in the Alzheimer's Disease Neuroimaging Initiative cohort also showed no association between LGMN and AD. These findings suggest that the LGMN gene may not be a critical factor for AD development.

The Roles of Long-Term Hyperhomocysteinemia and Micronutrient Supplementation in the AppNL–G–F Model of Alzheimer’s Disease

“…In contrast, a decreased serum concentration of LGMN was detected with the opposite result compared to the above proteins, i.e., deletion of LGMN is associated with the alleviation of synapse loss ( Zhang et al, 2014 ). However, a recent human trial did not confirm previous reports, according to which LGMN was a driver of the process of AD development ( Zhang et al, 2020 ). Interestingly, the present proteome analysis revealed that (neuro-) inflammatory pathways were affected by HHCys in both directions: aside from the elevation of pro-inflammatory IL1a serum level ( Dinarello, 2018 ), concentrations of other protein markers were decreased in comparison to KI control mice (IL23R, CCL2, CXCL9, S100A4, WISP1, and EDA2R), indicating also anti-inflammatory effects ( Teng et al, 2015 ; Verhelst et al, 2015 ; Martin and Delarasse, 2018 ; Ambartsumian et al, 2019 ; Chen and Li, 2020 ).…”

Combined proteomic and lipidomic studies in Pompe disease allow a better disease mechanism understanding

“…TTR and GSN, down regulated in PD, are known for their role in preventing the amyloid deposition, 71 an epiphenomenon reported in lysosomal storage diseases 72 . Moreover, down‐regulation of GSN, involved in actin filament, may be directly connected with the disrupted interactions between actin and myosin in PD muscles.…”

“…Finally, enrichment analysis of GO cellular components, showed that GPLD1 was attributed to lysosomal membrane, with a possible function in adapter protein recruitment and exocytosis. 70 TTR and GSN, down regulated in PD, are known for their role in preventing the amyloid deposition, 71 an epiphenomenon reported in lysosomal storage diseases. 72 Moreover, down-regulation of GSN, involved in actin filament, may be directly connected with the disrupted interactions between actin and myosin in PD muscles.…”

Mutations in GBA, SNCA, and VPS35 are not associated with Alzheimer’s disease in a Chinese population: a case-control study

“…Genomic DNA from peripheral blood leukocytes was isolated according to standard procedures as previously described (Jiao et al, 2014;Zhang et al, 2020). The DNA quality and quantity were assessed by both NanoDrop spectrophotometer 2000 (Thermo Scientific, Wilmington, DE, USA) and Qubit Fluorometer 3 (Life Technologies, Carlsbad, CA, USA).…”