TY - JOUR
T1 - Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer's disease
T2 - Review and hypothesis
AU - Qiu, Wei Qiao
AU - Folstein, Marshal F.
N1 - Funding Information:
W.Q.Q. thanks Dr. Dennis J. Selkoe for his encouragement to pursue the idea of Aβ degradation then the IDE work when she worked in his laboratory, and for his continuous support. The authors thank Peg AtKisson, Igna Peter, Timothy Liu, Drew Leins and Jacqui Yee for critically reading and editing the manuscript. This work was supported in part by grants from NIA, AG-022476 for W.Q.Q., AG-21790 for M.F.F., and by grants from GREFF award (GCRC of New England Medical Center) and NEMC recruitment fund for W.Q.Q.
PY - 2006/2
Y1 - 2006/2
N2 - Clinical and epidemiological studies have found that type 2 diabetes, and hyperinsulinaemia, increased the risk of developing Alzheimer's disease (AD) in the elderly. The link between hyperinsulinaemia and AD may be insulin-degrading enzyme (IDE). This enzyme degrades both insulin and amylin, peptides related to the pathology of type 2 diabetes, along with amyloid-β peptide (Aβ), a short peptide found in excess in the AD brain. We review the current evidence, which suggests that hyperinsulinaemia may elevate Aβ through insulin's competition with Aβ for IDE. Genetic studies have also shown that IDE gene variations are associated with the clinical symptoms of AD as well as the risk of type 2 diabetes. The deficiency of IDE can be caused by genetic variation or by the diversion of IDE from the metabolism of Aβ to the metabolism of insulin. It is intriguing to notice that both hyperinsulinaemia and IDE gene variations are related to the risk of AD when the Apolipoprotein E4 (ApoE4) allele, the major risk factor of late-onset AD, is not present. Further studies of the role of IDE in the pathogenesis of AD, which may uncover potential treatment target, are much needed.
AB - Clinical and epidemiological studies have found that type 2 diabetes, and hyperinsulinaemia, increased the risk of developing Alzheimer's disease (AD) in the elderly. The link between hyperinsulinaemia and AD may be insulin-degrading enzyme (IDE). This enzyme degrades both insulin and amylin, peptides related to the pathology of type 2 diabetes, along with amyloid-β peptide (Aβ), a short peptide found in excess in the AD brain. We review the current evidence, which suggests that hyperinsulinaemia may elevate Aβ through insulin's competition with Aβ for IDE. Genetic studies have also shown that IDE gene variations are associated with the clinical symptoms of AD as well as the risk of type 2 diabetes. The deficiency of IDE can be caused by genetic variation or by the diversion of IDE from the metabolism of Aβ to the metabolism of insulin. It is intriguing to notice that both hyperinsulinaemia and IDE gene variations are related to the risk of AD when the Apolipoprotein E4 (ApoE4) allele, the major risk factor of late-onset AD, is not present. Further studies of the role of IDE in the pathogenesis of AD, which may uncover potential treatment target, are much needed.
KW - Amyloid β-peptide
KW - Insulin
KW - Insulin-degrading enzyme
KW - Type 2 diabetes and Alzheimer's disease
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U2 - 10.1016/j.neurobiolaging.2005.01.004
DO - 10.1016/j.neurobiolaging.2005.01.004
M3 - Review article
C2 - 16399206
AN - SCOPUS:29844432266
SN - 0197-4580
VL - 27
SP - 190
EP - 198
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 2
ER -