Molecular Pathogenesis of Sporadic Alzheimer's Disease (AD) and Pharmaceutical Research to Develop a Biomarker for AD Diagnosis

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Saori Hata

Abstract

Alzheimer's disease (AD) is the most common senile dementia. One of the pathological characteristics of AD is the appearance of senile plaques composed of amyloid-β (Aβ) depositions. Aβ is generated by consecutive cleavages of Aβ precursor protein (APP) by β- and γ-secretases. The common pathogenesis for familial AD (FAD) is believed to involve misprocessing of APP by γ-secretase, resulting in increased Aβ42 peptide deposition. However, little is known about γ-secretase function in sporadic AD (SAD), which is the major type of AD. This may be because Aβ42 peptide has highly aggregative properties; therefore it is not easy to estimate the quantitative alteration of net Aβ42 in SAD patients. Alcadein is a family of neural type I membrane proteins. Processing of Alcadein by APP α- and γ-secretases results in secretion of non-aggregative peptide, p3-Alc, into CSF and blood. The C-terminuses of Aβ and p3-Alc are altered by FAD-linked genetic mutations in catalytic components of γ-secretase, in association with an increase in minor Aβ and p3-Alc species. Thus p3-Alcs are expected to behave as useful indicators of γ-secretase dysfunction in SAD brain. Quantitative and qualitative analyses of p3-Alcs raise the possibility that γ-secret...Continue Reading

References

Mar 24, 2004·The Journal of Biological Chemistry·Yoichi ArakiToshiharu Suzuki
Jan 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yue Qi-TakaharaYasuo Ihara
May 11, 2012·Journal of Alzheimer's Disease : JAD·Kenji KamogawaToshiharu Suzuki
May 10, 2013·PloS One·Yi PiaoToshiharu Suzuki
Dec 7, 2013·Journal of Alzheimer's Disease : JAD·Chiori OmoriUNKNOWN Japanese Alzheimer’s Disease Neuroimaging Initiative

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