Combining serum and urine biomarkers in the early diagnosis of mild cognitive impairment that evolves into Alzheimer’s disease in patients with the apolipoprotein E ε4 genotype

Abstract

Possession of the apolipoprotein E (APOE) ε4 genotype is a major predictor of progression to Alzheimer’s disease (AD), particularly in patients with mild cognitive impairment (MCI). However, the use of APOE genotyping in the diagnosis of MCI is limited due to its low sensitivity and specificity, which often results in a high false-positive rate. In this study, we found that there was a significant decrease in serum BDNF and notable increase in urine AD7c-NTP in MCI patients who harbored the APOE ε4 allele. Both serum BDNF and urine AD7c-NTP had higher positive predictive values and were more sensitive biomarkers of MCI. Additionally, a testing strategy employing serum BDNF and urine AD7c-NTP revealed increases in sensitivity, positive and negative predictive values, and predictive ability compared with the use of either biomarker alone, suggested that combinatorial detection might have great potential for translation to the clinic.     

Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2

1. Download : Download high-res image (232KB)
2. Download : Download full-size image

     

Concise and high-yield synthesis of T808 and T808P for radiosynthesis of [18F]-T808, a PET tau tracer for Alzheimer’s disease

The authentic standard T808 and its corresponding mesylate precursor T808P were synthesized in six steps using ethyl vinyl ether and trichlorocetyl chloride as starting materials. The overall chemical yields of T808 and T808P were 35% and 52%, respectively. [¹⁸F]-T808 was synthesized from T808P by the nucleophilic substitution with K[¹⁸F]F/Kryptofix 2.2.2 and isolated by HPLC combined with solid-phase extraction (SPE) purification in 35–45% radiochemical yield with 37–370 GBq/μmol specific activity at end of bombardment (EOB).     

Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M1 positive allosteric modulators

A series of methoxynaphthalene amides were prepared and evaluated as alternatives to quinolizidinone amide M₁ positive allosteric modulators. A methoxy group was optimal for M₁ activity and addressed key P-gp issues present in the aforementioned quinolizidinone amide series.     

Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans

1. Download : Download high-res image (186KB)
2. Download : Download full-size image

     

Positive association between soil arsenic concentration and mortality from alzheimer’s disease in mainland China

ObjectivesThe current study was designed to investigate the relationship between the soil arsenic (As) concentration and the mortality from Alzheimer’s disease (AD) in mainland China.Study designEcological study.MethodsTwenty-two provinces and 3 municipal districts in mainland China were included in this study. The As concentrations in soil in 1990 was obtained from the China State Environmental Protection Bureau; the data on annual mortality of AD from 1991 to 2000 were obtained from the National Death Cause Surveillance Database of China. Using these data, we calculated the spearman correlation coefficient between soil As concentration and AD mortality, and the relative risk (RR) between soil As levels and AD mortality by quartile-dividing study groups.ResultsThe spearman correlation coefficient between As concentration and AD mortality was 0.552 (p = 0.004), 0.616 (p = 0.001) and 0.622 (p = 0.001) in the A soil As (eluvial horizon), the C soil As (parent material horizon), and the Total soil As (A soil As + C soil As), respectively. When the A soil As concentration was over 9.05 mg/kg, 10.40 mg/kg and 13.10 mg/kg, the relative risk was 0.835 (95 % CI: 0.832, 0.838), 1.969 (95 %CI: 1.955, 1.982), and 2.939 (95 % CI: 2.920, 2.958), respectively; when the C soil As reached 9.45 mg/kg, 11.10 mg/kg and 13.55 mg/kg, the relative risk was 4.349 (95 % CI: 4.303, 4.396), 6.108 (95 % CI: 6.044, 6.172), and 9.125 (95 %CI: 9.033, 9.219), respectively. No correlation was found between lead, cadmium, and mercury concentration in the soil and AD mortality.ConclusionThere was an apparent soil As concentration dependent increase in AD mortality. Results of this study may provide evidence for a possible causal linkage between arsenic exposure and the death risk from AD.     

Recurrent dreams and psychosocial adjustment in preteenaged children.

Research indicates that recurrent dreams in adults are associated with impoverished psychological well-being. Whether similar associations exist in children remains unknown. The authors hypothesized that children reporting recurrent dreams would show poorer psychosocial adjustment than children without recurrent dreams. One hundred sixty-eight 11-year-old children self-reported on their recurrent dreams and on measures of psychosocial adjustment. Although 35% of children reported having experienced a recurrent dream during the past year, our hypothesis was only partially supported. Multivariate analyses revealed a marginally significant interaction between gender and recurrent dream presence and a significant main effect of gender. Univariate analyses revealed that boys reporting recurrent dreams reported significantly higher scores on reactive aggression than those who did not (d = 0.58). This suggests that by age 11 years, the presence of recurrent dreams may already reflect underlying emotional difficulties in boys but not necessarily in girls. Challenges in addressing this developmental question are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Novel multifunctional dopamine D2/D3 receptors agonists with potential neuroprotection and anti-alpha synuclein protein aggregation properties

Our ongoing drug development endeavor to design compounds for symptomatic and neuroprotective treatment of Parkinson’s disease (PD) led us to carry out a structure activity relationship study based on dopamine agonists pramipexole and 5-OHDPAT. Our goal was to incorporate structural elements in these agonists in a way to preserve their agonist activity while producing inhibitory activity against aggregation of α-synuclein protein. In our design we appended various catechol and related phenol derivatives to the parent agonists via different linker lengths. Structural optimization led to development of several potent agonists among which (−)-8a, (−)-14 and (−)-20 exhibited potent neuroprotective properties in a cellular PD model involving neurotoxin 6-OHDA. The lead compounds (−)-8a and (−)-14 were able to modulate aggregation of α-synuclein protein efficiently. Finally, in an in vivo PD animal model, compound (−)-8a exhibited efficacious anti-parkinsonian effect.