Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. The S18Y polymorphism of the UCHL1 gene confers protection against Parkinson's disease. In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE ε4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P = 0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD.

Analysis of a membrane‐enriched proteome from postmortem human brain tissue in Alzheimer's disease

“…Increased association of UCHL1 with the membrane fraction due to farnesylation has also been reported in Parkinson's disease and was shown to mediate alpha‐synuclein toxicity in cells []. While certain polymorphisms in UCHL1 are reported to be protective in Parkinson's disease, this protective effect is not seen in AD []. Given that UCHL1 appears to play a role in many neurodegenerative diseases, it is likely not specific to AD; however, that does not negate the fact that it may also play an important role in AD pathogenesis.…”

Lack of Genetic Association of the UCHL1 Gene with Alzheimer’s Disease and Parkinson’s Disease with Dementia

“…We found that the 5 SNPs studied here were in Hardy-Weinberg equilibrium and our LD analysis suggests that the gene consists of one LD block. Two previous studies showed no association between the UCHL1 S18Y polymorphism and Caucasian AD [15,18]. However, a study by Xue and Jia [19] on a Han Chinese population found that the Y allele of the polymorphism might have a protective effect for female AD cases only.…”

“…The effect of common UCHL1 polymorphisms on AD has not been fully explored either. Several studies on the relationship between S18Y and AD have been carried out, but its effect on AD is still unresolved [15]. …”

Biomarkers of injury to neural tissue in veterinary medicine

“…Tau is a highly soluble microtubule associated protein whose main function is to bind to microtubules, promoting their assembly and stability (35). Following injury, it is cleaved by calpain-1 and 3, becomes insoluble and forms aggregates, known as neurofibrillary tangles (80). Such tau inclusions were identified in numerous degenerative diseases, which were collectively named tauopathies (79).…”