The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice

Autophagy is the principal cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Recently, autophagy has been implicated in neurodegeneration, but whether it is detrimental or protective remains unclear. Here we report that beclin 1, a protein with a key role in autophagy, was decreased in affected brain regions of patients with Alzheimer disease (AD) early in the disease process. Heterozygous deletion of beclin 1 (Becn1) in mice decreased neuronal autophagy and resulted in neurodegeneration and disruption of lysosomes. In transgenic mice that express human amyloid precursor protein (APP), a model for AD, genetic reduction of Becn1 expression…

• JD
  John Douglas French Alzheimer's Foundation
• SU
  Shantou University Medical College
• NI
  National Institutes of Health

  Awards: AG5131, AG18440, AG20603, AG10435
• UO
  University of California, San Diego
• UO
  University of California, Irvine
• SB
  Stanford Bio-X
• GR
  Geriatric Research Education and Clinical Center
• NC
  NIH Clinical Center