Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Abstract

IntroductionBiomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1).Materials and MethodsIGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated.ResultsPD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters.DiscussionElevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

Is insulin-like growth factor-1 involved in Parkinson’s disease development?

“…These IGF-1 concentrations inversely correlate with the UPDRS-III score (i.e. with motor function), verbal episodic memory, visuoperceptual abilities and attention/ executive functions; been not found such correlation on healthy subjects [171][172][173][174][175][176][177][178][179][180][181]. As it has been shown, lower IGF-1 levels at the beginning of PD are associated with a worse disease progression and prognosis.…”

Epigenetic DNA Methylation Profiling with MSRE: A Quantitative NGS Approach Using a Parkinson's Disease Test Case

“…Even gastric and colonic mucosa have been profiled for markers (Chung et al, 2016). Blood is probably the most active area of PD marker research looking at a range of potential targets from IGF-I titers (Bernhard et al, 2016), micro-RNA signatures (Ding et al, 2016), mitochondrial densities (Pyle et al, 2016), vitamins (Ding et al, 2013; Ide et al, 2015), lymphocytes (Tan et al, 2014, 2016) and proteins like alpha-synuclein (SNCA) (Pihlstrøm et al, 2015). …”

Manganese and the Insulin-IGF Signaling Network in Huntington’s Disease and Other Neurodegenerative Disorders

“…While serum and plasma levels offer a potential biomarker of brain Mn dysregulation, further studies must examine how these levels correlate to what is seen in actual brain tissue. Studies have found that changes in IGF by age, sex, diet, BMI, and secondary disease status can cause immense variability between patients, particularly in peripheral samples 118 . Several heavy metals are reported to accumulate in the brain with age and can differ by similar confounds suggesting peripheral Mn may also be an inappropriate measurement for brain Mn.…”