**Author details**

Kohzo Nakayama1,4\*, Hisashi Nagase2 , Chang-Sung Koh3 and Takeshi Ohkawara1

\*Address all correspondence to: kohzona@shinshu-u.ac.jp

1 Department of Anatomy, Shinshu University, School of Medicine, Matsumoto, Nagano, Ja‐ pan

2 Department of Immunology and Infectious Diseases, Shinshu University, School of Medi‐ cine, Japan

3 Department of Biomedical Sciences, Shinshu University, School of Health Sciences, Matsu‐ moto, Nagano, Japan

4 Department of Developmental and Regenerative Medicine, Mie University, Graduate School of Medicine, Tsu, Mie, Japan

### **References**

IDE, insulin-degrading enzyme;

KPI, Kunitz inhibitor domain;

Pen-2, PS enhancer-2 protein;

RA, all-trans-retinoic acid;

TM, transmembrane;

**Acknowledgments**

155-166 (2012).

**Author details**

pan

cine, Japan

moto, Nagano, Japan

School of Medicine, Tsu, Mie, Japan

Kohzo Nakayama1,4\*, Hisashi Nagase2

\*Address all correspondence to: kohzona@shinshu-u.ac.jp

NICD, the intracellular domain of Notch;

RIP, regulated intramembrane proteolysis;

Our works described here were supported by the grants-in-aid from the Ministry of Edu‐ cation, Culture, Sports, Science, and Technology of Japan. Some parts of this manuscript have been taken from our publications in Cellular and Molecular Neurobiology Volume 31, Number 6, 887-900 (2011) and in Current Psychopharmacology, Volume 1, Number 2,

, Chang-Sung Koh3

1 Department of Anatomy, Shinshu University, School of Medicine, Matsumoto, Nagano, Ja‐

2 Department of Immunology and Infectious Diseases, Shinshu University, School of Medi‐

3 Department of Biomedical Sciences, Shinshu University, School of Health Sciences, Matsu‐

4 Department of Developmental and Regenerative Medicine, Mie University, Graduate

and Takeshi Ohkawara1

JM, juxtamembrane;

80 Understanding Alzheimer's Disease

NCT, nicastrin; NEP, neprilysin; PS, presenilin;


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**Chapter 5**

**Phosphorylation of Tau Protein Associated as a**

**Protective Mechanism in the Presence of Toxic, C-**

**Terminally Truncated Tau in Alzheimer's Disease**

Alzheimer's disease (AD) is the most common cause of dementia in the elderly and is char‐ acterized by progressive memory loss leading to a gradual and irreversible deterioration of cognitive function. The neuropathology of AD is characterized by the accumulation of fibril‐ lary lesions in the form of neuritic plaques (NPs, Fig. 1A), neurofibrillary tangles (NFTs, Fig. 1C,D; small arrow) and dystrophic neurites (DNs, Fig. 1; arrows) in neocortex, amygdala and hippocampus [1]. The density of the NPs and NFTs correlate with the degree of demen‐ tia in AD [2]. The accumulation of these lesions does not occur at random; the presence of NFTs is associated with vulnerability of the perforant pathway [3]. NPs are comprised of ex‐ tracellular deposits of amyloid-β peptide fibrils that are associated with DNs of dendritic and axonal origin (Fig. 1A; arrows). Intracellular NFTs selectively kill neurons in specific brain areas. In AD, the distribution of NFTs follows a stereotypical profile arising first in layer II of the entorhinal cortex, hippocampal region and CA1/subicular layer IV of the ento‐ rhinal cortex and then neocortex (mainly in fronto-temporal and parietal areas). This pattern of distribution was first described by Braak and Braak in 1991 [4], and provides the most im‐ portant neuropathological criteria for a definite diagnosis of AD (Fig. 2) [5]. Ultrastructural‐ ly, NFTs are composed of dense accumulations of structures known as paired helical

> © 2013 Luna-Muñoz 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.

> © 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,

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

José Luna-Muñoz, Charles R. Harrington, Claude M. Wischik, Paola Flores-Rodríguez,

Raúl Mena, Marco A. Meraz-Ríos and

Benjamin Floran-Garduño

http://dx.doi.org/10.5772/54228

**1. Introduction**

Jesús Avila, Sergio R. Zamudio, Fidel De la Cruz,

Additional information is available at the end of the chapter

