Brain region-specific myelinogenesis is not directly linked to amyloid-ß in APP/PS1 transgenic mice.
Exp Neurol
; 362: 114344, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36736651
ABSTRACT
Alzheimer's disease (AD) is characterized by aggregating amyloid beta-protein (Aß). Recent evidence has shown that insufficient myelinogenesis contributes to AD-related functional deficits. However, it remains unclear whether Aß, in either plaque or soluble form, could alter myelinogenesis in AD brains. By cell-lineage tracing and labeling, we found both myelinogenesis and Aß deposits displayed a region-specific pattern in the 13-month-old APP/PS1 transgenic mouse brains. Aß plaques cause focal demyelination, but only about 15% Aß plaques are closely associated with newly formed myelin in the APP/PS1 brains. Further, the Aß plaque total area and the amount of new myelin are not linearly correlated across different cortical regions, suggesting that Aß plaques induce demyelination but may not exclusively trigger remyelination. To understand the role of soluble Aß in regulating myelinogenesis, we chose to observe the visual system, wherein soluble Aß is detectable but without the presence of Aß plaques in the APP/PS1 retina, optic nerve, and optic tract. Interestingly, newly-formed myelin density was not significantly altered in the APP/PS1 optic nerves and optic tracts as compared to the wildtype controls, suggesting soluble Aß probably does not change myelinogenesis. Further, treatment of purified oligodendrocyte precursor cells (OPCs) with soluble Aß (oligomers) for 48 h did not change the cell densities of MBP positive cells and PDGFRα positive OPCs in vitro. Consistently, injection of soluble Aß into the lateral ventricles did not alter myelinogenesis in the corpus callosum of NG2-CreErt; Tau-mGFP mice significantly. Together, these findings indicate that the region-dependent myelinogenesis in AD brains is not directly linked to Aß, but rather probably a synergic result in adapting to AD pathology.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Desmielinizantes
/
Enfermedad de Alzheimer
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Exp Neurol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China