**Acknowledgements**

process in Alzheimer. Most potential experimental therapies exhibit the highest efficiency when applied during the pre-symptomatic phase of the disease. Therefore, it is essential to develop diagnostic tools to detect Alzheimer at early stages. Moreover, considering that Alzheimer, as a degenerative process not necessarily leading to dementia, affects a large percentage of individuals in the sixth decade of life, it would be wise to introduce habits and low-cost, safe treatments to prevent the progression of Alzheimer early in life, as occurs in artheriosclerosis, to transform AD into a chronic, incomplete and non-devastating disease

**Figure 1.** Schematic representation of the main cellular targets that are currently under development to prevent or retard the progression of Alzheimer to disease states. Most of the experimental approaches are designed to block or mitigate (red lines) pathological events occurring at the earliest stages, including abnormal Aβ and tau aggregation, chronic inflammatory responses, and oxidative stress damage. Other strategies (blue lines) aim at stimulating the me‐ tabolism to reduce Alzheimer's energetic failure as well as to promote intrinsic mechanisms that protect or repair cel‐ lular damage, including synaptic plasticity, preservation of the lipid membrane composition, and the promotion of damaged protein and organelle turnover. Therapeutic approaches based on the modulation of neurotransmission (green dashed lines) are designed to bypass deficient cholinergic neurotransmission whereas other compounds aim to block glutamatergic excitotoxicity. Considering the complex scenario of the Alzheimer neurodegenerative process,

In addition to these general conclusions, several points deserve a particular comment. Recognition of the genotypic background, clinical and neuropathological subtypes and different pace of clinical manifestations is important to refine personalized treatments [333-335]. This includes modifications of the treatment as Alzheimer is not a mere accu‐ mulation of defects but rather a combination of deficiencies and plastic changes that im‐ ply shifts in molecular pathways with disease progression. Drugs and treatments

multi-target therapies applied at early stages of the disease appear to be the most effective strategy.

thereby allowing for normal life in the elderly.

274 Understanding Alzheimer's Disease

Parts of the work used in this review were supported by the project BESAD-P (Instituto Carlos III), Mutua Madrileña and Agrupación Mútua. We wish to thank T. Yohannan for editorial assistance.
