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When an outsider enters in the field of Alzheimer's disease (AD) realizes that many of the therapeutic strategies tested (in animal models) have been successful. One also may notice that there is a general lack of real translational research and, although the obvious limitations of the animal models ...

When an outsider enters in the field of Alzheimer's disease (AD) realizes that many of the therapeutic strategies tested (in animal models) have been successful. One also may notice that there is a general lack of real translational research and, although the obvious limitations of the animal models available, efforts are still focused on novel projects to expand the therapeutic arsenal to "cure mice".

The reasons why there are so many successful strategies in phase 1 are not obvious. We think that is essential to open a debate to identify which common mechanisms of cognitive enhancement and neuroprotection are brought by different approaches.

To our knowledge, no similar strategy has been taken before. Thus, a specific Research Topic in Frontiers in Pharmacology may allow significant advances in dissecting out which are the overlapping mechanisms engaged by different drugs and/or approaches for treating AD. This would provide useful information to turn around the current negative output in generating effective drugs. Furthermore, a clear distinction between cognitive enhancers, neuroprotective and disease modifying strategies should be instrumental for the advance in the drug discovery to combat AD.

Putative contents:

Canonical approaches:
- The anti-amyloid approach (heavily explored even in clinical trials and with a very little –if any- success)
- The anti-tau approach

Atypical approaches:
- The insulin-diabetes link
- Antioxidants and phospholipids
- Dual cholinergic and serotonergic drugs
- Cognitive training
- G-protein-coupled receptors
- Antihypertensives
- Cholesterol
- Histone deacetylase inhibitors
- Phosphodiesterases

Conclusion articles:
- Cognitive enhancement versus neuroprotective and disease modifying strategies
- The cAMP/GPCR path
- The cAMP/cGMP/phosphodiesterase path
- The metabolic syndrome path
- The epigenetics path

General Conclusions article

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