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
Jan 16, 1999·The Journal of Biological Chemistry·S TomitaT Suzuki
Sep 16, 2003·The Journal of Biological Chemistry·Yoichi ArakiToshiharu Suzuki
Mar 24, 2004·The Journal of Biological Chemistry·Yoichi ArakiToshiharu Suzuki
Oct 20, 2004·Biochemistry·Satoru FunamotoYasuo Ihara
Jan 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yue Qi-TakaharaYasuo Ihara
Mar 3, 2007·The EMBO Journal·Yoichi ArakiToshiharu Suzuki
Oct 30, 2009·The Journal of Biological Chemistry·Saori HataToshiharu Suzuki
Jun 18, 2011·Annals of Neurology·Saori HataToshiharu Suzuki
Nov 10, 2011·Molecular Neurodegeneration·Tomoko KonnoUNKNOWN Japanese Alzheimer's Disease Neuroimaging Initiative
Apr 27, 2012·Molecular Neurodegeneration·Saori HataUNKNOWN Japanese Alzheimer's Disease Neuroimaging Initiative
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
Nov 20, 2014·The Journal of Biological Chemistry·Norio TakeiToshiharu Suzuki