Table 1.
Ongoing developments for AD treatment and therapies.
| Possible disease-modifying treatment | Substance example | Results | References |
|---|---|---|---|
| α secretase activators | Etazolate, Epigallocatechin gallate | Safety, Aβ aggregation↓ | Vellas et al., 2011; Schneider et al., 2014 |
| β secretase inhibitors | Pioglitazone, rosiglitazone, AZD3293 | Safety, Plasma Aβ concentration↓cognitive benefit for diabetic patients in an observational study, until now no prospective clinical effect | Geldmacher et al., 2011; Read et al., 2014; Schneider et al., 2014; Heneka et al., 2015a,b; Cebers et al., 2017; Galimberti and Scarpini, 2017 |
| γ secretase modulators | Tarenflurbil, EVP-0962 | No clinical effect | Green et al., 2009; Morimoto, 2010; Schneider et al., 2014 |
| γ secretase inhibitors | Semagacestat, Avagacestat | Skin cancer↑, infections↑, no clinical effect | Coric et al., 2012; Tong et al., 2012; Schneider et al., 2014 |
| Aβ aggregation inhibitors | PBT2, Tramiprosat, Scylloinositol | CSF Aβ ↓, PiB PET↓, no clinical effect | Lannfelt et al., 2008; Faux et al., 2010; Schneider et al., 2014 |
| Aβ active immunotherapy | Anti-Aβ vaccines AN1792, CAD-106 | Meningoencephalitis (AN1792), positive antibody response, no clinical effect | Gilman et al., 2005; Winblad et al., 2012; Schneider et al., 2014; Farlow et al., 2015; Vandenberghe et al., 2017 |
| Aβ passive immunotherapy | Solanezumab, Bapineuzumab | Safety, questionable cognitive effect of Solanezumab | Schneider et al., 2014; Siemers et al., 2016; Mo et al., 2017; Honig et al., 2018 |
| τ phosphorylation inhibitors | Lithium, valproate | High toxicity, CSF τ ↓, and questionable cognitive effect of Lithium | Hampel et al., 2009; Forlenza et al., 2011; Schneider et al., 2014 |
| τ fibrillization inhibitors | Methylene blue, davunetide | τ production ↓, possible cognitive effect of davunetide | Morimoto et al., 2013; Schneider et al., 2014 |
| Macro-/Micronutrients | Polyunsaturated fatty acids | No clinical effect | Freund-Levi et al., 2006, 2009; Quinn et al., 2010; Schneider et al., 2014 |
| Phosphodiesterase inhibitors | Cilostazol | Possible cognitive effect | Arai and Takahashi, 2009; Schneider et al., 2014 |
| Tyrosine kinase inhibitors | Masitinib | unclear | Schneider et al., 2014; Folch et al., 2015 |
| Statines | Simvastatin, atorvastatin | Unclear cognitive effects, CSF phopsho-τ ↓ | Sano et al., 2011; Schneider et al., 2014; Li et al., 2017 |
| Insulin | Intranasal insulin | FDG PET effect, possible cognitive effect | Craft et al., 2012; Schneider et al., 2014 |
| NGF intracerebral application | Neurotrophic growth factor | CSF effects, gene expression effects, possible cognitive effect in the subgroup | Wahlberg et al., 2012; Tuszynski et al., 2015; Eyjolfsdottir et al., 2016 |
| Deep brain stimulation | n.a. | Possible cognitive effects, highly invasive, ethical issues | Hardenacke et al., 2013; Salma et al., 2014; Nardone et al., 2015; Bittlinger and Muller, 2018; Lv et al., 2018 |
| Transcranial brain stimulation | n.a. | Unclear effects | Freitas et al., 2011; Floel, 2014; Nardone et al., 2014, 2015; Rowan et al., 2014; Lefaucheur et al., 2017 |