| First Author | González-Marrero I | Year | 2015 |
| Journal | Front Cell Neurosci | Volume | 9 |
| Pages | 17 | PubMed ID | 25705176 |
| Mgi Jnum | J:242460 | Mgi Id | MGI:5905258 |
| Doi | 10.3389/fncel.2015.00017 | Citation | Gonzalez-Marrero I, et al. (2015) Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease. Front Cell Neurosci 9:17 |
| abstractText | Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Abeta) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer's disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: beta-amyloid (Abeta) plaques and neurofibrillary tangles (NFT) with a temporal- and regional- specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Abeta in AD. This study analyzed the effects of highly-expressed AD-linked human transgenes (APP, PS1 and tau) on lateral ventricle CP function. Confocal imaging and immunohistochemistry revealed an increase only of Abeta42 isoform in epithelial cytosol and in stroma surrounding choroidal capillaries; this buildup may reflect insufficient clearance transport from CSF to blood. Still, there was increased expression, presumably compensatory, of the choroidal Abeta transporters: the low density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end product (RAGE). A thickening of the epithelial basal membrane and greater collagen-IV deposition occurred around capillaries in CP, probably curtailing solute exchanges. Moreover, there was attenuated expression of epithelial aquaporin-1 and transthyretin (TTR) protein compared to Non-Tg mice. Collectively these findings indicate CP dysfunction hypothetically linked to increasing Abeta burden resulting in less efficient ion transport, concurrently with reduced production of CSF (less sink action on brain Abeta) and diminished secretion of TTR (less neuroprotection against cortical Abeta toxicity). The putative effects of a disabled CP-CSF system on CNS functions are discussed in the context of AD. |
