BACKGROUND: Hyperinsulinemia and insulin resistance are risk factors for memory impairment and Alzheimer disease (AD). Insulin regulates levels of the amyloid beta-peptide (Abeta) in vitro in neuronal cultures and in vivo in the CSF of normal older adults. OBJECTIVE: To determine whether insulin affected plasma Abeta 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 Abeta 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 Abeta 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 Abeta 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 beta-peptide (Abeta) elevation. Abnormal regulation of peripheral Abeta by insulin may contribute to AD risk.
BACKGROUND:Hyperinsulinemia and insulin resistance are risk factors for memory impairment and Alzheimer disease (AD). Insulin regulates levels of the amyloid beta-peptide (Abeta) in vitro in neuronal cultures and in vivo in the CSF of normal older adults. OBJECTIVE: To determine whether insulin affected plasma Abeta 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 Abeta 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 Abeta 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 Abeta 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 beta-peptide (Abeta) elevation. Abnormal regulation of peripheral Abeta by insulin may contribute to AD risk.
Authors: Michael Malek-Ahmadi; Thomas Beach; Aleksandra Obradov; Lucia Sue; Christine Belden; Kathryn Davis; Douglas G Walker; LihFen Lue; Abdu Adem; Marwan N Sabbagh Journal: Curr Alzheimer Res Date: 2013-07 Impact factor: 3.498
Authors: Fei Song; Anne Poljak; Michael Valenzuela; Richard Mayeux; George A Smythe; Perminder S Sachdev Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472
Authors: Yasuji Matsuoka; Howard F Andrews; Amanda G Becker; Audrey J Gray; Pankaj D Mehta; Mary C Sano; Arthur J Dalton; Paul S Aisen Journal: Alzheimer Dis Assoc Disord Date: 2009 Oct-Dec Impact factor: 2.703
Authors: Olivier Thibault; Katie L Anderson; Chris DeMoll; Lawrence D Brewer; Philip W Landfield; Nada M Porter Journal: Eur J Pharmacol Date: 2013-07-17 Impact factor: 4.432
Authors: O L Lopez; L H Kuller; P D Mehta; J T Becker; H M Gach; R A Sweet; Y F Chang; R Tracy; S T DeKosky Journal: Neurology Date: 2008-04-09 Impact factor: 9.910