| First Author | Lee MK | Year | 2024 |
| Journal | Int J Mol Sci | Volume | 25 |
| Issue | 9 | PubMed ID | 38732223 |
| Mgi Jnum | J:348370 | Mgi Id | MGI:7640638 |
| Doi | 10.3390/ijms25095004 | Citation | Lee MK, et al. (2024) Loss of Cholinergic and Monoaminergic Afferents in APPswe/PS1DeltaE9 Transgenic Mouse Model of Cerebral Amyloidosis Preferentially Occurs Near Amyloid Plaques. Int J Mol Sci 25(9) |
| abstractText | Alzheimer's disease (AD) is characterized by a loss of neurons in the cortex and subcortical regions. Previously, we showed that the progressive degeneration of subcortical monoaminergic (MAergic) neurons seen in human AD is recapitulated in the APP(swe)/PS1DeltaE9 (APP/PS) transgenic mouse model. Because degeneration of cholinergic (Ach) neurons is also a prominent feature of AD, we examined the integrity of the Ach system in the APP/PS model. The overall density of Ach fibers is reduced in APP/PS1 mice at 12 and 18 months of age but not at 4 months of age. Analysis of basal forebrain Ach neurons shows no loss of Ach neurons in the APP/PS model. Thus, since MAergic systems show overt cell loss at 18 months of age, the Ach system is less vulnerable to neurodegeneration in the APP/PS1 model. We also examined whether the proximity to Abeta deposition affected the degeneration of Ach and 5-HT afferents. We found that the areas closer to the edges of compact Abeta deposits exhibit a more severe loss of afferents than the areas that are more distal to Abeta deposits. Collectively, the results indicate that the APP/PS model recapitulates the degeneration of multiple subcortical neurotransmitter systems, including the Ach system. In addition, the results indicate that Abeta deposits cause global as well as local toxicity to subcortical afferents. |
