Table 1.
Summary of preclinical and clinical studies on the efficacy of anti-diabetic, insulin-sensitizing drugs on multiple aspects of AD pathology in human patients and animal models.
| Compound | Finding | Model | References |
|---|---|---|---|
| Insulin | Prevention of AβO induced synapse loss and IR reduction; amelioration of PKR-mediated ER stress | Rat hippocampal neuronal cultures | De Felice et al., 2009; Lourenco et al., 2013. |
| Insulin | AD patients that are not ε4 carriers have reduced sensitivity to insulin, affecting cognitive performance | AD patients homozygous or not for the apoE-ε4 allele and normal subjects intravenously injected | Craft et al., 2003. |
| Insulin | Improve verbal memory in MCI AD ε4- subjects after acute insulin administration but not in ε4 carriers | AD patients homozygous or not for the apoE-ε4 allele, mild cognitive impaired patients and normal subjects intranasally administrated | Reger et al., 2006, 2008a |
| Insulin | Chronic intranasal insulin doses enhanced selective attention, retention of new information and functional status of MCI and early AD subjects | AD patients, mild cognitive impaired patients and normal subjects intranasally administrated | Reger et al., 2008b |
| Insulin | Only women presented improved working memory after treatment | Healthy men and woman intranasally administrated | Benedict et al., 2008 |
| Liraglutide | Reduction of tau phosphorylation; prevention of IR reduction and synapse loss in a c-AMP dependent manner | Cynomolgus monkeys injected icv with AβO | Batista et al., 2018 |
| Liraglutide | Improvement of memory deficits in novel object recognition test and fear conditioning | Swiss mice injected icv with AβO | Batista et al., 2018 |
| Liraglutide | Restore memory deficits in object regonition test and morris water maze; enhance LTP; Reduce microglial activation; diminish amyloid plaque load | APP/PS1 mice | McClean et al., 2011; McClean and Hölscher, 2014 |
| Exendin-4 | Decrease of the inhibitory phosphorylation of Ser312IRS1, Ser636IRS1 and of JNK, while restoring activating Tyr465IRS1 phosphorylation | Rat hippocampal neural cultures | Bomfim et al., 2012. |
| Exendin-4 | Improvement of spatial memory in moris water maze; reduced amyloid plaque load | APP/PS1 mice | Bomfim et al., 2012 |
| Exendin-4 Liraglutide | eIF2α phosphorylation reduction | Rat hippocampal neural cultures, APP/PS1 mice, cynomolgus monkeys injected icv with AβO | Lourenco et al., 2013 |
| GLP-1 Exendin-4 | Reduction of neural excitotoxicity | Rat hippocampal neural cultures; Rats injected on the basal nucleus with ibotenic acid | Perry, 2002 |
| Rosiglitazone | Reversal of memory deficits in object recognition test and morris water maze; Aβ levels reduction | AD transgenic mice J20 line | Escribano et al., 2010 |