Prodromal Alzheimer’s disease: Constitutive upregulation of neuroglobin prevents the initiation of Alzheimer’s pathology

In humans, a considerable number of the autopsy samples of cognitively normal individuals aged between 57 and 102 years have revealed the presence of amyloid plaques, one of the typical signs of AD, indicating that many of us use mechanisms that defend ourselves from the toxic consequences of Aß. The human APP NL/F (hAPP NL/F) knockin mouse appears as the ideal mouse model to identify these mechanisms, since they have high Aß42 levels at an early age and moderate signs of disease when old. Here we show that in these mice, the brain levels of the hemoprotein Neuroglobin (Ngb) increase with age, in parallel with the increase in Aß42. In vitro, in wild type neurons, exogenous Aß increases the expression of Ngb and Ngb over-expression prevents Aß toxicity. In vivo, in old hAPP NL/F mice, Ngb knockdown leads to dendritic tree simplification, an early sign of Alzheimer’s disease. These results could indicate that Alzheimer’s symptoms may start developing at the time when defense mechanisms start wearing out. In agreement, analysis of plasma Ngb levels in aged individuals revealed decreased levels in those whose cognitive abilities worsened during a 5-year longitudinal follow-up period.This work was partially supported by the Stichting Alzheimer Onderzoek (SAO; S16013) and the FWO (research project G0B2519N) to LC-G, SAF2016-76722 (AEI/FEDER, UE) to CD, Marie Skłodowska-Curie Actions – Individual Fellowships (T2DMand AD, EU 708152) to FG and EU JPND “EpiAD” Grant to AF-G and CD, SAF2016-78603-R to MM and M

Design of an algorithm for the diagnostic approach of patients with joint pain

Background Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. Objective To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. Methods Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point “joint pain” as a common symptom for the four diseases. Results Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. Conclusion We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain