| First Author | Marin MA | Year | 2016 |
| Journal | Exp Neurol | Volume | 281 |
| Pages | 93-8 | PubMed ID | 27109181 |
| Mgi Jnum | J:236737 | Mgi Id | MGI:5807007 |
| Doi | 10.1016/j.expneurol.2016.04.018 | Citation | Marin MA, et al. (2016) Amyloid-beta plaques disrupt axon initial segments. Exp Neurol 281:93-8 |
| abstractText | UNLABELLED: Amyloid-beta (Abeta) plaques are one of the central pathologies of Alzheimer's disease (AD). Plaque formation in animal models of AD coincides with the appearance of synaptic abnormalities, aberrant neuronal excitability, and cognitive decline. Abeta plaques may disrupt neuronal excitability since they have been proposed to be synaptotoxic, to induce axonal varicosities and neurite breakage, and to significantly decrease spine density. Axon initial segments (AIS) also regulate neuronal excitability and help maintain neuronal polarity. Despite these essential functions, the effects of plaques on AIS structure have not been fully determined. Using a mouse AD model, we measured a significant decrease in the density of AIS up to 75mum away from the center of fibrillar, thioflavin-labeled plaques. The reduction was observed in animals with both moderate and severe plaque loads, and was associated with increased densities of microglia near the plaques. Furthermore, animals with severe plaque loads had significantly reduced AIS lengths adjacent to Abeta plaques. These results suggest the local environment surrounding Abeta plaques may be harmful to the AIS. We propose that AIS loss is a previously unappreciated consequence of AD that could significantly impact brain function. SIGNIFICANCE STATEMENT: This paper demonstrates that neurons near Abeta plaques have disrupted axon initial segments. Loss or disruption of AIS is predicted to have detrimental consequences for brain function. |
