Alzheimer's disease and diabetes: new insights and unifying therapies.
Several research groups have begun to associate the Alzheimer Disease (AD) to Diabetes Mellitus (DM), obesity and cardiovascular disease. This relationship is so close that some authors have defined Alzheimer Disease as Type 3 Diabetes. Numerous studies have shown that people with type 2 diabetes have twice the incidence of sporadic AD. Insulin deficiency or insulin resistance facilitates cerebral β-amyloidogenesis in murine model of AD, accompanied by a significant elevation in APP (Amyloid Precursor Protein) and BACE1 (β-site APP Cleaving Enzime 1). Similarly, deposits of Aβ produce a loss of neuronal surface insulin receptors and directly interfere with the insulin signaling pathway. Furthermore, as it is well known, these disorders are both associated to an increased cardiovascular risk and an altered cholesterol metabolism, so we have analyzed several therapies which recently have been suggested as a remedy to treat together AD and DM. The aim of the present review is to better understand the strengths and drawbacks of these therapies.
Department of Clinical Science, Section of Biochemistry, Universita Politecnica delle Marche, Via Tronto 10 A, 60020 Ancona, Italy.
Arianna
A
Vignini
Alessia
A
Giulietti
Laura
L
Nanetti
Francesca
F
Raffaelli
Lucia
L
Giusti
Laura
L
Mazzanti
Leandro
L
Provinciali
D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000097:blood; D016282:Aspartic Acid Endopeptidases / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D011972:Receptor, Insulin / Q000378:metabolism*; D012307:Risk Factors; D016875:tau Proteins / Q000097:blood
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D016875:tau Proteins; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D011972:Receptor, Insulin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human