| First Author | Krivinko JM | Year | 2022 |
| Journal | Alzheimers Dement (N Y) | Volume | 8 |
| Issue | 1 | Pages | e12324 |
| PubMed ID | 36016832 | Mgi Jnum | J:351738 |
| Mgi Id | MGI:7663144 | Doi | 10.1002/trc2.12324 |
| Citation | Krivinko JM, et al. (2022) Fingolimod mitigates synaptic deficits and psychosis-like behavior in APP/PSEN1 mice. Alzheimers Dement (N Y) 8(1):e12324 |
| abstractText | INTRODUCTION: Current treatments for psychosis in Alzheimer's disease (AD), a syndrome characterized by more rapid deterioration and reduced synaptic protein abundance relative to non-psychotic AD, are inadequate. Fingolimod, a currently US Food and Drug Administration (FDA)-approved pharmacotherapy for multiple sclerosis, alters synaptic protein expression and warrants preclinical appraisal as a candidate pharmacotherapy for psychosis in AD. METHODS: Presenilin and amyloid precursor protein transgenic mice (APPswe/PSEN1dE9) and wild-type mice were randomized to fingolimod or saline for 7 days. Psychosis-associated behaviors were quantified by open field testing, pre-pulse inhibition of the acoustic startle response testing, and habituation of the acoustic startle response testing. Synaptic proteins were quantified by liquid chromatography/mass spectrometry in homogenate and postsynaptic density fractions. RESULTS: Fingolimod treatment increased the synaptic protein abundance in cortical homogenates and normalized psychosis-associated behaviors in APPswe/PSEN1dE9 mice relative to saline. Mitochondrial-related proteins were preferentially altered by fingolimod treatment and correlated with improvements in psychosis-associated behaviors. DISCUSSION: Preclinical studies employing complementary psychosis-associated behavioral assessments and proteomic evaluations across multiple AD-related models are warranted to replicate the current study and further investigate fingolimod as a candidate treatment for psychosis in AD. |
