2-pentadecyl-2-oxazoline prevents cognitive and social behaviour impairments in the Amyloid ß-induced Alzheimer-like mice model: Bring the α2 adrenergic receptor back into play.

The 2-pentadecyl-2-oxazoline (PEA-OXA) is a natural compound with protective action in neuro-inflammation. We have previously shown that PEA-OXA behaves as an α2 adrenergic receptor (α2AR) antagonist and a putative protean agonist on histamine H3 receptors. Recently, neuroinflammation and monoaminergic neurotransmission dysfunction has drawn particular attention in Alzheimer Disease (AD) pathophysiology. In this context, the objective of this study was to investigate the effects of the dual-acting PEA-OXA in an AD-like model in mice. A combined computational and experimental approach was used to evaluate the ability of PEA-OXA to bind α2A-AR subtype, and to investigate the effects of PEA-OXA treatment on neuropathological (behavioural and functional) effects induced by soluble Amyloid ß 1-42 (sAß1-42) intracerebroventricular injection. Computational analysis revealed the PEA-OXA ability to bind the α2A-AR, a pharmacological target for AD, in two alternative poses, one overlapping the Na+ binding site. In vivo studies indicated that chronic treatment with PEA-OXA (10 mg/kg, os) restored the cognitive (discriminative and spatial memory) deficits and social impairments induced by sAß injection. Consistently, electrophysiological analysis showed a recovery of the long-term potentiation in the hippocampus (Lateral Entorhinal Cortex-Dentate Gyrus pathway), while neuroinflammation, i.e., increased pro-inflammatory cytokines levels and microglia cells density were reduced. These data provide the basis for further investigation of the pro-cognitive aptitude of PEA-OXA by proposing it as an adjuvant in the treatment in AD, for which the available pharmacological approaches remain unsatisfactory. Moreover, this study offers new future direction in research investigating the role of α2AR in neuropsychiatric illness and therapies.

Cuantificación absoluta de la captación miocárdica de 99mTc-DPD en pacientes con amiloidosis cardiaca por depósitos de transtiretina (ATTR) / Absolute quantification of myocardial uptake of 99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR)

Objetivo Determinar la contribución diagnóstica de la cuantificación absoluta del depósito miocárdico de 99mTc-DPD en pacientes con amiloidosis cardiaca por depósitos de transtiretina (ATTR). Materiales y métodos Se realizó SPECT/TC a 41 pacientes con resultado gammagráfico positivo para amiloidosis cardiaca ATTR. Se dividió a los pacientes en dos grupos (grados2 y3 de Perugini) y se calcularon los SUVmax a nivel del hueso y de ambos ventrículos y el porcentaje de dosis calculado en estas áreas. Se empleó la prueba t de Student para comparar resultados y se calculó el área bajo la curva (AUC) para evaluar la eficacia diferencial y establecer unos puntos de corte discriminatorios entre ambos grupos de pacientes. Resultados Se observaron diferencias estadísticamente significativas en todas las variables a estudio, a excepción del SUVmax hueso. Las diferencias con mayor potencia estadística se observaron en las variables SUVmaxVD y el porcentaje de dosis en ambos ventrículos (p<0,001). El punto de corte obtenido para la variable SUVmaxVI fue de 8,620 (sensibilidad del 87,9% y especificidad del 100%; AUC: 0,966), mientras que el de la variable SUVmaxVD fue de 6,195 (sensibilidad del 81,8% y especificidad del 100%; AUC: 0,955). Conclusiones La cuantificación absoluta de la captación miocárdica de 99mTc-DPD en las imágenes SPECT/TC de pacientes con sospecha de amiloidosis cardiaca por depósitos de transtiretina supone una nueva herramienta diagnóstica que permite una adecuada clasificación de los pacientes, acorde a la escala de gradación visual de Perugini (AU)

Purpose To determine the diagnostic contribution of the absolute quantification of the myocardial deposit of 99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR). Materials and methods SPECT/CT was performed on 41 patients with positive scintigraphic results for ATTR cardiac amyloidosis. The patients were divided into two groups (Perugini grades2 and3) and the SUVmax at the level of the bone and both ventricles and the percentage of dose calculated in these areas were calculated. Student's t-test was used to compare results and the area under the curve (AUC) was calculated to assess differential efficacy and establish discriminatory cut-off points between both groups of patients. Results Statistically significant differences were observed in all the study variables, with the exception of SUVmax bone. The differences with the greatest statistical power were observed in the variables SUVmaxRV and the percentage of dose in both ventricles (P<.001). The cut-off point obtained for the variable SUVmaxLV was 8.620 (sensitivity 87.9% and specificity 100%; AUC: 0.966), while that of the variable SUVmaxRV was 6.195 (sensitivity 81.8% and specificity 100%; AUC: 0.955). Conclusions The absolute quantification of myocardial uptake of 99mTc-DPD in the SPECT/CT images of patients with suspected cardiac amyloidosis due to transthyretin deposits represents a new diagnostic tool that allows an adequate classification of patients, according to the visual grading scale of Perugini (AU)