Plasma cyclic-glycine-proline/IGF-1, a potential biomarker for circulating IGF-1 function and its applications in neurological conditions

Abstract

Circulating insulin-like growth factor-1 (IGF-1) has a role in stroke and maintenance of cognition. Therefore, biomarkers for circulating IGF-1 function may assist the monitoring and prognosis of stroke recovery and progression of cognitive impairment in diseases, such as Parkinson’s disease (PD). Current biomarkers for IGF-1 function are not reliable and an alternative is cyclic-glycine-proline (cGP)/IGF-1 molar ratio, which potentially could be applied to neurological conditions. This thesis investigates the relationship of plasma cGP/IGF-1 with stroke recovery and cognitive impairment in PD. The oral bioavailability of cGP-rich blackcurrant anthocyanin (BCA) is also investigated. The concentration of cGP, IGF-1 and insulin growth factor binding protein-3 (IGFBP-3) were measured using ELISA and HPLC-MS in: 1) plasma collected from stroke patients (n = 34) within 3 days of stroke onset (baseline), 7 days and 90 days after stroke and controls. 2) plasma from PD patients across the range of cognitive function, normal cognitive function (PD-N, n = 74), mild cognitive impairment (PD-MCI, n = 71) and dementia (PD-D, n = 33), and controls (n = 23). And 3) plasma and cerebrospinal fluid (CSF) from idiopathic PD patients with normal cognition (n = 10) before and after a 28-day supplementation with BCA. In stroke patients, baseline cGP/IGF-1 was lower compared to the controls, then gradually increased over the initial 90 days of stroke recovery, paralleled with improved neurological scores. High baseline cGP/IGF-1 predicted improved NIHSS score. In PD, plasma cGP/IGF-1 was positively associated with age in PD-N and negatively associated with age in PD-D. Plasma IGF-1 or IGF-1/IGFBP-3 did not change during stroke recovery and had no altered relationship with age in PD. Following the BCA supplementation, CSF cGP increased by around 20 %. These data suggest plasma cGP/IGF-1 molar ratio as a new biomarker for circulating IGF-1 function and its potential application to stroke and cognitive status in PD. Given that stroke and cognition are closely related to cerebrovascular function and integrity, this biomarker may be applicable to other neurological conditions with changes in cerebral vascular function. cGP is oral bioavailable. These findings would benefit from replication in larger cohorts with longer follow-up.