| First Author | Barrett T | Year | 2019 |
| Journal | Neuroscience | Volume | 417 |
| Pages | 45-56 | PubMed ID | 31421203 |
| Mgi Jnum | J:282995 | Mgi Id | MGI:6384467 |
| Doi | 10.1016/j.neuroscience.2019.08.017 | Citation | Barrett T, et al. (2019) p35 Hemizygous Deletion in 5xFAD Mice Increases Abeta Plaque Load in Males but Not in Females. Neuroscience 417:45-56 |
| abstractText | Increased amyloid beta (Abeta) deposition is implicated in early stages of Alzheimer's disease (AD). Although aberrant Cdk5 activity mediated by Cdk5/p25 is suggested to promote Abeta plaque deposition, the effects of Cdk5 inhibition on Abeta plaque loads in AD mouse models have been equivocal, possibly due to the fact that Cdk5 can be activated by p35 or p39 and their cleaved products. Here we evaluated the effect of p35 knockdown on Abeta plaque formation by constitutively knocking out a single p35 allele in 5xFAD mice. Surprisingly, our results show that the simultaneous reduction in the levels of p35 and p25 increases cortical Abeta plaque loads in male 5xFAD mice, but not in females. This change is associated with male specific decrease in pSer9 GSK3beta levels. Furthermore, p35 hemizygous deletion has sexually dimorphic effects on Iba1 and GFAP protein levels. Our findings demonstrate sex differences in the effects of p35 reduction on biochemical pathways relevant to the modulation of Abeta plaque deposition and confirm the importance of examining both sexes in preclinical AD research. |
