Insulin increases CSF Aβ42 levels in normal older adults

Background: Abnormal insulin metabolism may contribute to the clinical symptoms and pathophysiology of AD. In vitro studies show that insulin enhances the release of beta- amyloid protein ( Abeta) or inhibits its degradation, either of which might increase amyloid burden. Methods: On separate mornings, 16 healthy older adults ( 10 women, 6 men; mean age 68.7 years, SD 8.6 years) each underwent two infusions consisting of either saline ( placebo) or insulin ( 1.0 mU. kg(-1).min(-1)) plus dextrose to maintain euglycemia. After 120 minutes of infusion, blood, CSF, and cognitive measures were acquired. Results: As expected, insulin infusion produced an increase in CSF insulin concentration. Insulin infusion also led to an increase in CSF Abeta42 levels, most notably in older subjects. As has been observed previously, insulin infusion facilitated declarative memory, but such facilitation was attenuated in the subjects with the greatest increase in CSF Abeta42 levels. Conclusions: These findings are consistent with recent in vitro studies of insulin effects on Abeta and support the notion that insulin may modulate Abeta42 levels acutely in humans.