Research interests centre around physiology of ageing of cerebrospinal fluid (CSF) dynamics and blood-brain barrier.

We have previously studied the role of ageing in CSF clearance of Amyloid-β (1-40) and the main findings indicated that with age, Aβ did not undergo the rapid removal from CSF seen in young animals, but was retained in CSF and brain (Preston 2001). In addition, the choroid plexuses forming the blood-CSF barrier avidly accumulated and degraded excess Ab in young animals, but the aged barrier was unable to increase degradation and showed down-regulation in mitochondrial activity suggestive of toxicity (Preston et al 2004). These studies led the research focus more generally toward ageing of the blood-CSF barrier, fundamental to the handling of a range of potential neurotoxins.

We have found age-related changes in CSF production and blood-CSF barrier function which would predispose to ‘stagnation’ of CSF and subsequent brain accumulation of any compound found in the fluid (Chen et al 2005, Neurobiol. Aging). There is also down-regulation of de novo protein synthesis by the choroid plexus, including reduced synthesis and CSF content of the protein transthyretin (Chen et al 2003, Chen et al 2005, J. Geront.), which is both a thyroxine binding protein, and also a chelator of Ab and prevents neurotoxicity. Ongoing research is using 2-D gel proteomics to identify biomarkers for ageing, e.g. ↓ transthyretin, which may increase risk of late life neurodegeneration (Preston et al 2004, Redzic et al 2005, Chen et al 2004). A second theme concerns poor early nutrition in utero, and risk of late life hypertension and diabetes using a rat model, funded by the British Heart Foundation.