**Author details**

José Luna-Muñoz1 , Charles R. Harrington2 , Claude M. Wischik2 , Paola Flores-Rodríguez1 , Jesús Avila3 , Sergio R. Zamudio4 , Fidel De la Cruz4 , Raúl Mena1 , Marco A. Meraz-Ríos5 and Benjamin Floran-Garduño1

1 Departments of Physiology, Biophysics and Neurosciences, National Laboratory of experi‐ mental services (LaNSE), CINVESTAV-IPN, Mexico

2 Division of Applied Health Sciences, School of Medicine and Dentistry, University of Aberdeen, USA

3 Centro de Biología Molecular ''Severo Ochoa'', CSIC/UAM, Universidad Autónoma de Madrid, Madrid, Spain

4 Department of Physiology, ENCB-IPN, Mexico

5 Molecular Biomedicine, CINVESTAV-IPN, Mexico

### **References**

**Figure 7.** Scheme illustrating the early steps of aggregation and polymerization of tau protein in Alzheimer´s disease. (A) The model starts with the appearance of PHF-core tau in cytoplasm of susceptible neurons. (B) The high binding capacity of PHF-tau results in the assembly of dimers of PHF-core and intact tau molecules in the cytoplasm. (C) The phosphorylation of intact tau would be an early event to hide the toxic soluble aggregates of molecules. (D). The high affinity and stability of the proto-filaments that make up the mature intracellular NFT allows tau molecules to form PHFs. (E) With the death of the neuron, the PHF-core subunit becomes exposed again in the extracellular space follow‐

Authors express their gratitude to the Mexican families for the donation of brain tissue from their beloved and without which these studies would not be possible. Amparo Viramontes Pintos for the handling of brain tissue.This work was financially supported by CONACyT

ing proteolysis. Further details are described in the text.

**Acknowledgements**

100 Understanding Alzheimer's Disease

grants, No. 142293 (to B.F.).


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106 Understanding Alzheimer's Disease

**Chapter 6**

**Pin1 Protects Against Alzheimer's Disease:**

Alzheimer's disease (AD] is the most common form of dementia, and it accounts for more than 60% of all cases of dementia. Although many factors may increase the risk for AD, the only cause so far known is aging [1]. Most of the cases are sporadic, as only less than 0.1% of the cases occur because of inherited mutations on genes directly involved in the disease (familial AD, FAD] [2].

AD is caused by progressive and irreversible neurodegeneration. At the moment, there is no cure for AD. Therapies available are only aimed at lessening the progression of the cognitive decline and neurodegeneration and do not target pathways directly causative of the disease [3]. These include the acetylcholinesterase inhibitors (Aricept] [4] or inhibitors of the gluta‐ matergic NMDA receptor (Namenda] [5] and were shown to be mostly effective when administered at early stages [6-8]. However, a proper diagnostic approach able to identify AD early in the development is still missing, and this reduces the efficacy of the treatments available. Therefore, there is the need to develop both diagnostic tools able to detect early stages of the disease, and to generate effective treatments targeting the early pathogenic events in AD. This is becoming increasingly important also considering that the population affected by AD will dramatically increase in the years to come. Numbers are in fact dramatic: 10 million baby boomers may develop AD within the next 10-20 years [9]. Currently, in the United States alone there are more than 5 million AD patients, and the costs to the US government exceeds the 200 billion/year.These numbers are expected to quadruple in the next 40 years, causing unsustainable costs for the care of these patients and their caregivers, who could not receive

> © 2013 Pastorino et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

support and care and would then have to face undignified life conditions.

**One Goal, Multiple Mechanisms**

Additional information is available at the end of the chapter

Kun Ping Lu

**1. Introduction**

http://dx.doi.org/10.5772/55085

**1.1. Plaque and tangle pathology in AD**

Lucia Pastorino, Asami Kondo, Xiao Zhen Zhou and
