Document Detail

Amyloid-β production via cleavage of amyloid-β protein precursor is modulated by cell density.
MedLine Citation:
PMID:  20847415     Owner:  NLM     Status:  MEDLINE    
Mounting evidence suggests that Alzheimer's disease (AD) is caused by the accumulation of the small peptide, amyloid-β (Aβ), a proteolytic cleavage product of amyloid-β protein precursor (AβPP). Aβ is generated through a serial cleavage of AβPP by β- and γ-secretase. Aβ40 and Aβ42 are the two main components of amyloid plaques in AD brains, with Aβ42 being more prone to aggregation. AβPP can also be processed by α-secretase, which cleaves AβPP within the Aβ sequence, thereby preventing the generation of Aβ. Little is currently known regarding the effects of cell density on AβPP processing and Aβ generation. Here we assessed the effects of cell density on AβPP processing in neuronal and non-neuronal cell lines, as well as mouse primary cortical neurons. We found that decreased cell density significantly increases levels of Aβ40, Aβ42, total Aβ, and the ratio of Aβ42: Aβ40. These results also indicate that cell density is a significant modulator of AβPP processing. Overall, these findings carry profound implications for both previous and forthcoming studies aiming to assess the effects of various conditions and genetic/chemical factors, e.g., novel drugs on AβPP processing and Aβ generation in cell-based systems. Moreover, it is interesting to speculate whether cell density changes in vivo may also affect AβPP processing and Aβ levels in the AD brain.
Can Zhang; Andrew Browne; Jason R Divito; Jesse A Stevenson; Donna Romano; Yuanlin Dong; Zhongcong Xie; Rudolph E Tanzi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  22     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2010  
Date Detail:
Created Date:  2010-11-22     Completed Date:  2011-03-09     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  683-984     Citation Subset:  IM    
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MeSH Terms
Amyloid Precursor Protein Secretases / metabolism
Amyloid beta-Peptides / metabolism*
Amyloid beta-Protein Precursor / drug effects,  genetics,  metabolism*
Cell Count* / methods
Cells, Cultured
Cerebral Cortex / cytology
Enzyme-Linked Immunosorbent Assay / methods
Molecular Weight
Neurons / metabolism
Peptide Fragments / metabolism*
Protein Processing, Post-Translational*
Protein Structure, Tertiary
Grant Support
5T32AG000222-18/AG/NIA NIH HHS; R37 MH060009/MH/NIMH NIH HHS; R37 MH060009-13/MH/NIMH NIH HHS
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Peptide Fragments; 0/amyloid beta-protein (1-40); 0/amyloid beta-protein (1-42); EC 3.4.-/Amyloid Precursor Protein Secretases

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