Differential modulation of plasma β-amyloid by insulin in patients with Alzheimer disease

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Abstract
Background: Hyperinsulinemia and insulin resistance are risk factors for memory impairment and Alzheimer disease (AD). Insulin regulates levels of the amyloid β-peptide (Aβ) in vitro in neuronal cultures and in vivo in the CSF of normal older adults. Objective: To determine whether insulin affected plasma Aβ levels and whether such effects differed for patients with AD compared with normal older adults. Methods: Fifty-nine patients with AD and 50 healthy older adults each received infusions of saline and of insulin (1.0 mU · kg−1 · min−1) with accompanying dextrose to maintain euglycemia. A subset of participants (19 AD, 12 normal) received two additional conditions, in which insulin was infused at a lower (0.33 mU · kg−1 · min−1) and higher (1.67 mU · kg−1 · min−1) rate. Plasma insulin and Aβ were measured after 120 minutes of infusion. Results: Adults with AD had higher plasma insulin vs normal adults at the two higher infusion rates, despite receiving comparable amounts of insulin. For normal adults, insulin reduced plasma Aβ levels at the middle (1.0 mU · kg−1 · min−1) dose, with attenuated effects at lower and higher doses. In contrast, for patients with AD, insulin raised plasma Aβ levels at the two higher doses (1.0 and 1.67 mU · kg−1 · min−1). Conclusions: These results suggest that patients with Alzheimer disease (AD) have reduced insulin clearance and insulin-provoked plasma amyloid β-peptide (Aβ) elevation. Abnormal regulation of peripheral Aβ by insulin may contribute to AD risk.