Differential Effects of the Interaction Between the Education and APOE ε4 Allele on Amyloid-beta Retention and Memory Performances in Cognitively Normal Older Adults and Alzheimer's Disease Patients.

BACKGROUND: Despite the effect of education and APOE ε4 allele on amyloid-beta (Aß) retention and memory, previous studies have not dealt with an interaction between two factors on Aß deposition and memory function in the course of Alzheimer's disease (AD). OBJECTIVE: To evaluate education by APOE ε4 allele interactions for Aß retention and neuropsychological test scores in cognitively normal older adults without Aß deposition [CN(Aß-), n=45] and Alzheimer's disease patients with Aß retention [AD(Aß+), n=33]. METHODS: Multiple regression analyses (adjusted for age, gender) were conducted to examine the effects of education, APOE ε4 allele, and the interaction between the two factors on global, regional Aß load quantified using [18F]flutemetamol standardized uptake value ratio with the pons as a reference region, and on neuropsychological test scores in each group. RESULTS: The interaction between education and APOE ε4 allele had an effect on amyloid load in parietal lobes (uncorrected p<0.05) and striatum (Bonferroni corrected p<0.05) in each CN(Aß-) and AD(Aß+). There was also an interaction effect of education and APOE ε4 allele on the memory performance in each CN(Aß-) and AD(Aß+) (uncorrected p<0.05). APOE ε4 carriers of both groups showed opposing slopes with each other in the correlation between the education years and Aß load, memory performance. CONCLUSION: The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.

Versatile O-GlcNAc transferase assay for high-throughput identification of enzyme variants, substrates, and inhibitors.

The dynamic glycosylation of serine/threonine residues on nucleocytoplasmic proteins with a single N-acetylglucosamine (O-GlcNAcylation) is critical for many important cellular processes. Cellular O-GlcNAc levels are highly regulated by two enzymes: O-GlcNAc transferase (OGT) is responsible for GlcNAc addition and O-GlcNAcase (OGA) is responsible for removal of the sugar. The lack of a rapid and simple method for monitoring OGT activity has impeded the efficient discovery of potent OGT inhibitors. In this study we describe a novel, single-well OGT enzyme assay that utilizes 6 × His-tagged substrates, a chemoselective chemical reaction, and unpurified OGT. The high-throughput Ni-NTA Plate OGT Assay will facilitate discovery of potent OGT-specific inhibitors on versatile substrates and the characterization of new enzyme variants.

Optimizing the selectivity of DIFO-based reagents for intracellular bioorthogonal applications.

One of the most commonly employed bioorthogonal reactions with azides is copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC, a 'click' reaction). More recently, the strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC, a copper-free 'click' reaction) was developed, in which an alkyne is sufficiently strained to promote rapid cycloaddition with an azide to form a stable triazole conjugate. In this report, we show that an internal alkyne in a strained ring system with two electron-withdrawing fluorine atoms adjacent to the carbon-carbon triple bond reacts to yield covalent adducts not only with azide moieties but also reacts with free sulfhydryl groups abundant in the cytosol. We have identified conditions that allow the enhanced reactivity to be tolerated when using such conformationally strained reagents to enhance reaction rates and selectivity for bioorthogonal applications such as O-GlcNAc detection.

Posttraumatic hemidystonia treated with unilateral globus pallidus interna stimulation: Long-term follow-up and radiologic features.

OBJECTIVE: Hemidystonia is a unilateral clinical presentation of dystonia, and it is usually refractory to current methods of medical treatment. Recently, deep brain stimulation has given some hope of recovery to dystonic patients. MATERIALS AND METHODS: A 30-year-old right-handed man with no abnormal perinatal history or family history of movement disorders was admitted to our institution. The patient had suffered right-sided dystonia for more than three years after severe head trauma sustained four years prior. RESULTS: We performed a stereotactic implantation of an electrode into the left globus pallidus internus (GPi) and he showed excellent response to pallidal stimulation during long-term follow-up. CONCLUSIONS: We present a unique case of secondary posttraumatic hemidystonia treated with contralateral GPi stimulation with an excellent outcome. Pallidal stimulation can be a good treatment option for posttraumatic hemidystonia in selected cases.