Neurology 2003;60:1899-1903
© 2003 American Academy of Neurology
Insulin increases CSF Aß42 levels in normal older adults
G. S. Watson, PhD,
E. R. Peskind, MD,
S. Asthana, MD,
K. Purganan, BS,
C. Wait, BS,
D. Chapman, BSN,
M. W. Schwartz, MD,
S. Plymate, MD and
S. Craft, PhD
From the Geriatric Research, Education, and Clinical Center (Drs. Watson, Plymate, and Craft, K. Purganan, C. Wait, and D. Chapman) and Mental Illness Research, Education, and Clinical Center (Dr. Peskind), Veterans Affairs Puget Sound Health Care System, and Departments of Psychiatry and Behavioral Sciences (Drs. Watson, Peskind, and Craft, K. Purganan, C. Wait, and D. Chapman) and Medicine (Drs. Schwartz and Plymate), University of Washington School of Medicine, Seattle; and Geriatric Research, Education, and Clinical Center (Dr. Asthana), William S. Middleton Memorial Veterans Hospital, and Department of Medicine (Dr. Asthana), University of Wisconsin Medical School, Madison.
Address correspondence and reprint requests to Dr. S. Craft, S-182-GRECC, VAPSHCS, 1660 S. Columbian Way, Seattle, WA, 98108; e-mail: scraft{at}u.washington.edu
Background: Abnormal insulin metabolism may contribute to the clinical symptoms and pathophysiology of AD. In vitro studies show that insulin enhances the release of ß-amyloid protein (Aß) 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 Aß42 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 Aß42 levels.
Conclusions: These findings are consistent with recent in vitro studies of insulin effects on Aß and support the notion that insulin may modulate Aß42 levels acutely in humans.
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