The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression

BMC Mol Biol. 2019 Oct 1;20(1):23. doi: 10.1186/s12867-019-0140-0.


Background: The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aβ. After the administration of Aβ1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aβ1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aβ1-40 generation.

Results: The administration of Aβ1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aβ1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aβ1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aβ.

Conclusions: The mechanism by which exogenous Aβ1-42 induces BACE1 expression and Aβ generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aβ generation in APPsw transgenic cells.

Keywords: Alzheimer’s disease; Aβ; BACE1-AS; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Aspartic Acid Endopeptidases / metabolism*
  • Brain / metabolism*
  • Cell Line, Tumor
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • RNA, Long Noncoding / physiology*
  • RNA, Messenger / metabolism


  • Amyloid beta-Peptides
  • BACE1-AS long non-coding RNA, human
  • Peptide Fragments
  • RNA, Long Noncoding
  • RNA, Messenger
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • long non-coding RNA BACE1-AS, mouse
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Bace1 protein, mouse