Abstract
Psychosis in Alzheimer's disease (AD+P) represents a distinct clinical and neurobiological AD phenotype and is associated with more rapid cognitive decline, higher rates of abnormal behaviors, and increased caregiver burden compared with AD without psychosis. On a molecular level, AD+P is associated with greater reductions in the protein kalirin, a guanine exchange factor which has also been linked to the psychotic disease, schizophrenia. In this study, we sought to determine the molecular and behavioral consequences of kalirin reduction in APPswe/PSEN1dE9 mice. We evaluated mice with and without kalirin reduction during tasks measuring psychosis-associated behaviors and spatial memory. We found that kalirin reduction in APPswe/PSEN1dE9 mice significantly attenuated psychosis-associated behavior at 12 months of age without changing spatial memory performance. The 12-month-old APPswe/PSEN1dE9 mice with reduced kalirin levels also had increased levels of the active, phosphorylated forms of p21 protein (Cdc42/Rac)–activated kinases (PAKs), which function in signaling pathways for maintenance of dendritic spine density, morphology, and function.
Original language | English (US) |
---|---|
Pages (from-to) | 59-70 |
Number of pages | 12 |
Journal | Neurobiology of Aging |
Volume | 54 |
DOIs | |
State | Published - Jun 1 2017 |
Keywords
- Alzheimer disease
- Kalirin
- Psychosis
ASJC Scopus subject areas
- Neuroscience(all)
- Aging
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology