No abstract

The objective of our study was to examine the relationship between the presence of the apolipoprotein E (apo E) epsilon 4 allele, psychiatric symptoms, and extrapyramidal signs (EPS) in probable Alzheimer's disease (AD). The apo E epsilon 4 allele modifies the risk and age at onset of AD. However, it still needs to be determined whether it is a marker for specific clinical subgroups. The frequency of clinical signs and symptoms was examined in 194 AD patients with the apo E epsilon 3/3 (N = 79), epsilon 3/4 (N = 96), and epsilon 4/4 (N = 19) genotypes participating in a longitudinal study of dementia. Each patient was assessed with semistructured psychiatric and neurologic examinations. Patients with the epsilon 4/4 genotype had an earlier age at onset of dementia (p = 0.03). However, no individual psychiatric symptom or neurologic sign was associated with the presence of the apo E epsilon 4 allele, including major depression (odds ratio [OR], 1.14; CI, 0.50 to 2.45; p = 0.78), psychosis (e.g., delusions and hallucinations) (OR, 0.66, CI, 0.35 to 1.25; p = 0.20), and EPS (in neuroleptic-free patients) (OR, 0.82, CI, 0.45 to 1.49; p = 0.52), after controlling by age at onset, duration of the symptoms, education, and severity of dementia. The presence of the apo E epsilon 4 allele has limited utility in the characterization of neurologic and psychiatric subgroups in probable AD patients. The apo E epsilon 4/4 genotype appears to be related to age at onset of AD, consistent with previous findings.

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.

Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD) and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. Regulatory regions relevant for SNCA expression include the 3 0 untranslated region (UTR), which among other regulatory elements contains several micro-RNA-binding sites. Interestingly, variants located in the 3 0 region of SNCA have been associated with PD in two genome-wide association studies. To test whether private mutations in this region contribute to PD, we sequenced the 3 0 UTR of SNCA in 1285 PD patients and 1120 age/sex-matched healthy controls. We found two rare variants, the one corresponding to the single nucleotide polymorphism rs145304567 and the novel variant c.*1004_1008delTTTTT. Although rs145304567 affects the putative-binding site of microRNA (miRNA) -433, the allele distribution was similar in PD patients and controls, and the expression of SNCA mRNA was not related to the genotype. Furthermore, a regulatory effect of miRNA-433 on SNCA expression levels was not detected.

CAS using the right transradial approach for left CAS in bovine-type aortic arch or the right transradial approach in type-III aortic arch for right CAS appears to be safe and technically feasible.