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. Th...

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Bibliographic Details
Published in:Frontiers in neuroscience 2020-12, Vol.14, p.562581
Main Authors: de Vidania, Silvia, Palomares-Perez, Irene, Frank-García, Ana, Saito, Takashi, Saido, Takaomi C, Draffin, Jonathan, Szaruga, María, Chávez-Gutierrez, Lucía, Calero, Miguel, Medina, Miguel, Guix, Francesc X, Dotti, Carlos G
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid
Amyloid-beta peptide
Antibodies
Autopsy
Cognitive ability
Dementia
dendritic complexity
Deoxyribonucleic acid
DNA
Heparan sulfate
Laboratory animals
Mutation
Neurodegenerative diseases
Neuroglobin
Neuroscience
Overexpression
Pathology
Peptides
Physiology
resilience
Senile plaques
Toxicity
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Summary: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 wild type neurons, exogenous Aß increases the expression of Ngb and Ngb over-expression prevents Aß toxicity. , 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.
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2020.562581