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Acetylcholinesterase Protein Level Is Preserved in the Alzheimer's Brain

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Abstract

Acetylcholinesterase (AChE) is a key enzyme in the cholinergic nervous system and is one of the most studied proteins in the field of Alzheimer's disease (AD). Moreover, alternative functions of AChE unrelated with the hydrolysis of acetylcholine are suspected. Until now, the majority of investigations on AChE in AD pathology have been focused on the determination of its enzymatic activity level, which is depleted in the AD brain. Despite this overall decrease, AChE activity increases at the vicinity of the two hallmarks of AD, the amyloid plaques and the neurofibrillary tangles (NFT). In fact, AChE may directly interact with Aβ in a manner that increases the deposition of Aβ to form plaques. In the context of protein–protein interactions, we have recently reported that AChE can interact with presenilin-1, the catalytic component of γ-secretase, influencing its expression level and also its activity. However, the alteration of AChE protein in the AD brain has not been determined. Here, we demonstrated by Western blotting and immunohistochemistry that a prominent pool of enzymatically inactive AChE protein existed in the AD brain. The potential significance of these unexpected levels of inactive AChE protein in the AD brain was discussed, especially in the context of protein–protein interactions with β-amyloid and presenilin-1.

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Acknowledgments

We thank Drs. A. Rábano (Fundación CIEN, Spain), I. Ferrer (Servicio de Anatomía Patológica, IDIBELL-Hospital Universitario de Bellvitge, Barcelona, Spain), and R. Alcaraz (Instituto Vasco de Medicina Legal, Bilbao, Spain) for assistance with human brain samples. We also thank Dr. Javier Defelipe (Laboratorio Cajal de Circuitos Corticales, Universidad Politécnica de Madrid, Spain) for technical facilities and advice. MLC is supported by a Consolider-Predoctoral fellowship from the CSIC, Spain. This work was supported by grants from Fundación CIEN-Reina Sofía, Fondo de Investigaciones Sanitarias (FIS; Grant PS09/00684) from Spain to JSV and Fondo de Investigaciones Sanitarias (FIS; Grant CP11/00312) to MSGA.

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Authors and Affiliations

  1. Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d’Alacant, 03550, Alicante, Spain

    María-Letizia Campanari, María-Salud García-Ayllón & Javier Sáez-Valero

  2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) http://www.ciberned.es/

    María-Letizia Campanari, María-Salud García-Ayllón & Javier Sáez-Valero

  3. Unidad de Investigación, Hospital General Universitario de Elche, FISABIO, Elche, Spain

    María-Salud García-Ayllón

  4. Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Campus Montegancedo, Pozuelo de Alarcón, Madrid, Spain

    Lidia Blazquez-Llorca

  5. Instituto Cajal (CSIC), Madrid, Spain

    Lidia Blazquez-Llorca

  6. Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China

    Wilson K. W. Luk & Karl Tsim

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  1. María-Letizia Campanari
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  2. María-Salud García-Ayllón
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  6. Javier Sáez-Valero
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Correspondence to Javier Sáez-Valero.

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Campanari, ML., García-Ayllón, MS., Blazquez-Llorca, L. et al. Acetylcholinesterase Protein Level Is Preserved in the Alzheimer's Brain. J Mol Neurosci 53, 446–453 (2014). https://doi.org/10.1007/s12031-013-0183-5

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