| First Author | Wu SL | Year | 2023 |
| Journal | Exp Neurol | Volume | 362 |
| Pages | 114344 | PubMed ID | 36736651 |
| Mgi Jnum | J:353713 | Mgi Id | MGI:7433970 |
| Doi | 10.1016/j.expneurol.2023.114344 | Citation | Wu SL, et al. (2023) Brain region-specific myelinogenesis is not directly linked to amyloid-beta in APP/PS1 transgenic mice. Exp Neurol 362:114344 |
| abstractText | Alzheimer's disease (AD) is characterized by aggregating amyloid beta-protein (Abeta). Recent evidence has shown that insufficient myelinogenesis contributes to AD-related functional deficits. However, it remains unclear whether Abeta, in either plaque or soluble form, could alter myelinogenesis in AD brains. By cell-lineage tracing and labeling, we found both myelinogenesis and Abeta deposits displayed a region-specific pattern in the 13-month-old APP/PS1 transgenic mouse brains. Abeta plaques cause focal demyelination, but only about 15% Abeta plaques are closely associated with newly formed myelin in the APP/PS1 brains. Further, the Abeta plaque total area and the amount of new myelin are not linearly correlated across different cortical regions, suggesting that Abeta plaques induce demyelination but may not exclusively trigger remyelination. To understand the role of soluble Abeta in regulating myelinogenesis, we chose to observe the visual system, wherein soluble Abeta is detectable but without the presence of Abeta 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 Abeta probably does not change myelinogenesis. Further, treatment of purified oligodendrocyte precursor cells (OPCs) with soluble Abeta (oligomers) for 48 h did not change the cell densities of MBP positive cells and PDGFRalpha positive OPCs in vitro. Consistently, injection of soluble Abeta 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 Abeta, but rather probably a synergic result in adapting to AD pathology. |
