Abstract
Alzheimer's disease (AD) is the most common type of dementia. Since there is no successful treatment for this devastating disease, more mechanistic studies are required to understand cause and progression of AD. More than ten years ago, it was suggested that formation of the cdk5 activator p25 is a critical step for neurodegeneration in AD. This claim was based on post-mortem studies that observed increased p25 expression in AD. However, these findings could not be replicated by other laboratories. Furthermore, in some transgenic mouse models mild p25 overexpression was shown not to induce neurodegeneration, but to enhance memory formation. This finding together with the assumption that p25 is formed in AD, suggested the Early Compensation Hypothesis, claiming that in the early stages of AD p25 is beneficial for cognition, whilst it would contribute to neurodegeneration in the later stages of AD. However, a recent systematic post-mortem analysis showed that p25 expression is reduced in the early stages of AD. Closer inspection of earlier post-mortem analysis confirms a downregulation of p25 expression in AD. Furthermore, in mice p25 formation is not an exclusively pathological process, as it is induced during spatial memory formation. Taken together, it has emerged that p25 formation is a memory mechanism that is impaired already in the early stages of AD.
| Original language | English |
|---|---|
| Title of host publication | Advances in Cognitive and Behavioral Sciences |
| Publisher | Nova Science Publishers Inc |
| Pages | 107-140 |
| Number of pages | 34 |
| ISBN (Electronic) | 9781629488936 |
| ISBN (Print) | 9781629488905 |
| Publication status | Published - 1 Jan 2014 |
Keywords
- Alzheimer's disease
- Cdk5
- Neurodegeneration
- p25
- P35
- Synaptic plasticiy