IGFBP3, which is the main binding target of IGF-1, plays an important role in regulating the activity and transport of IGF-1, and was reported to be independently associated with AF in the elderly population in the System-IGF-1 Pathway and Alzheimer’s Disease Clinical Trial (SIGAL) (54). Here, IGFBP3 is linked to early-onset autosomal dominant Alzheimer disease.