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From the Geriatric Research, Education, and Clinical Centers (Drs. Craft, Peskind, and Schellenberg), Mental Health Service (Drs. Peskind and Raskind), and Department of Medicine (Drs. Schwartz and Porte), Veteran Affairs Puget Sound Health Care System, Seattle, WA; and the Departments of Psychiatry and Behavioral Sciences (Drs. Craft, Peskind, and Raskind), Medicine (Drs. Schwartz and Porte), Pharmacology (Dr. Schellenberg), and Neurology (Dr. Schellenberg), University of Washington School of Medicine, Seattle, WA.
Address correspondence and reprint requests to Dr. Suzanne Craft, GRECC 182B, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108.
Patients with Alzheimer's disease (AD) have elevations of fasting plasma insulin that are hypothesized to be associated with disrupted brain insulin metabolism. We examined paired fasted plasma and CSF insulin levels in 25 patients with AD and 14 healthy age-matched adults and determined whether insulin levels were related to severity of dementia and apolipoprotein E-
4 homozygosity, a known genetic risk factor for AD. The AD patients had lower CSF insulin, higher plasma insulin, and a reduced CSF-to-plasma insulin ratio when compared with healthy adults. The differences were greater for patients with more advanced AD. Patients who were not apolipoprotein E-4 homozygotes had higher plasma insulin levels and reduced CSF-to-plasma ratios, whereas 4 homozygotes with AD had normal values. Both plasma and CSF insulin levels are abnormal in AD, and there are metabolic differences among apolipoprotein E genotypes.
Supported by the Department of Veteran Affairs, National Institute of Aging grants AG-10880 (to S.C.), AG-08419 (to M.R.), and AG-05136 (to M.R., E.P., and G.D.S.), Alzheimer's Association IIRG-95-1151 (to S.C.), NS 32273(to M.S.), and DK 12829 (to M.S. and D.P.).
Received March 17, 1997. Accepted in final form July 23, 1997.
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