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Relative Ratio and Level of Amyloid-β 42 Surrogate in Cerebrospinal Fluid of Familial Alzheimer Disease Patients with Presenilin 1 Mutations.
MedLine Citation:
PMID:  24192669     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Presenilin 1 (PS1) mutations associated with familial Alzheimer disease (FAD) generally increase the amyloid-β 42 (Aβ42) to Aβ40 ratio secreted in cultured cells. Some of these mutants reduce the secretion of Aβ40 rather than increase that of Aβ42. Since it has been difficult to estimate Aβ42 secretion in brains of PS1-FAD patients due to substantial Aβ42 accumulation, it remains unknown whether the enhanced Aβ42 to Aβ40 ratio in brains of FAD patients is caused by elevated Aβ42 secretion or by reduced secretion of Aβ40. Objective/Methods: Cerebrospinal fluids (CSF) of PS1-FAD patients and neurological control patients (controls) were collected. Levels of CSF amyloid precursor-like protein-1-derived Aβ-like peptide (APL1β), including APL1β28, an Aβ42 surrogate marker, were quantified by liquid chromatography tandem mass spectrometry, and Aβ42 secretion in the brain was estimated. Results: The relative ratio of CSF APL1β28 to total APL1β was higher in PS1-FAD patients than in controls. Importantly, CSF APL1β28 was not significantly higher. However, C-terminally shorter CSF APL1β25 and APL1β27 were significantly lower in PS1-FAD patients and, as expected, so were CSF Aβ40 and Aβ42. Conclusion: A higher relative ratio of the CSF Aβ42 surrogate in PS1-FAD patients is not due to its increase in CSF, suggesting that massive Aβ42 accumulation in the PS1-FAD brain occurs without an apparent increase in Aβ42 secretion. © 2013 S. Karger AG, Basel.
Authors:
Shinji Tagami; Masayasu Okochi; Kanta Yanagida; Takashi Kodama; Tetsuaki Arai; Ryozo Kuwano; Takeshi Ikeuchi; Masatoshi Takeda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-30
Journal Detail:
Title:  Neuro-degenerative diseases     Volume:  -     ISSN:  1660-2862     ISO Abbreviation:  Neurodegener Dis     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-11-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101189034     Medline TA:  Neurodegener Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Neuropsychiatry and Neurochemistry, Division of Internal Medicine, Department of Integrated Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
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