Abstract
Insulin-like growth factor 1 (IGF-1) serum levels have been reported to be altered in Alzheimer’s disease patients, and it was suggested that the changes in IGF-1 serum level may play a role in disease pathology and progression. However, this notion remained controversial due to conflicting findings. We conducted a meta-analysis to determine the relationship between IGF-1 serum levels and Alzheimer’s disease. We searched the databases PUBMED, Ovid SP, and Cochrane library for relevant studies. The primary data analyzed was serum IGF-1 from Alzheimer’s disease subjects and controls. Pooled weighted mean difference using a random effects model was used to determine the relationship between serum levels and disease state. Nine studies were included in the meta-analysis compromising a total of 1639 subjects. The pooled weighted mean difference was -2.27ng/ml (95% CI: [-22.221, 17.66]) with a P value of 0.82. Thus our finding did not show clear relationship between low IGF-1 and Alzheimer’s disease subjects. We did not find evidence of publication bias by analyzing a funnel plot as well as Egger’s and Begg’s tests. While eight out of the nine studies included in this meta-analysis detected a statistically significant increase or decrease in serum levels of IGF-1 in Alzheimer’s disease subjects, the analysis as a whole did not show a significant trend in either direction. Thus, IGF-1 level is likely a critical personalized factor. A large database of clinical trials is required for better understanding the relationship between IGF-1 levels and Alzheimer’s disease.
Highlights
Insulin-like growth factor 1 (IGF-1) is a 7.5kDa peptide hormone produced primarily in the liver and in smaller quantities in other organs such as the brain [1]
Serum IGF-1 is increased in amyloid precursor protein (APP), APP/presenilin 1 (PS1), and 3xTG transgenic mouse models [38, 42]
To better understand whether IGF-1 is a protective agent in Alzheimer’s disease (AD), we identified a total of 3540 studies from the database search, yielding 10 studies that provided serum IGF-1 values that could be used for analysis (Fig 1)
Summary
Insulin-like growth factor 1 (IGF-1) is a 7.5kDa peptide hormone produced primarily in the liver and in smaller quantities in other organs such as the brain [1]. IGF-1 production in the liver is regulated by growth hormone secreted by the pituitary gland, while regulation in other tissues is not yet fully understood. IGF-1 binds to a family of insulin-like growth factor binding proteins (IGBPs) that extend its serum half-life. The primary target of IGF-1 is the IGF-1 receptor (IGF-1R), but can activate the insulin receptor [2]. Downstream targets of IGF-1R include activation of the MAPK/ERK and PI3K/AKT pathways, PLOS ONE | DOI:10.1371/journal.pone.0155733. Downstream targets of IGF-1R include activation of the MAPK/ERK and PI3K/AKT pathways, PLOS ONE | DOI:10.1371/journal.pone.0155733 May 26, 2016
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