Prodromal Alzheimer’s Disease: Constitutive Upregulation of Neuroglobin Prevents the Initiation of Alzheimer’s Pathology

Frontiers in Neuroscience

Miguel Medina¹  Miguel Calero¹  Takaomi C. Saido²  Ana Frank-García³  Lucía Chávez-Gutierrez⁴  María Szaruga⁴  Takashi Saito⁵  Silvia de Vidania⁶  Carlos G. Dotti⁶  Irene Palomares-Perez⁶  Jonathan Draffin⁶  Francesc X. Guix⁶ 

[1] CIBERNED, Queen Sofia Foundation Alzheimer Center, CIEN Foundation, Instituto de Salud Carlos III, Madrid, Spain;Department of Neurocognitive Science, Nagoya City University Graduate School of Medical Science, Nagoya, Japan;Department of Neurology, Instituto de Salud Carlos III (ISCIII), Division Neurodegenerative Disease, University Hospital La Paz, Madrid, Spain;KU Leuven Department for Neurosciences, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium;Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako-shi, Japan;Molecular Neuropathology, Physiological and Pathological Processes, Centro de Biología Molecular Severo Ochoa, CSIC/UAM, Madrid, Spain;

关键词: Alzheimer’s disease;    Amyloid-beta peptide;    dendritic complexity;    neuroglobin;    resilience;   

DOI  :  10.3389/fnins.2020.562581

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown