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Ann Clin Transl Neurol. 2015 Jul;2(7):769-73. doi: 10.1002/acn3.211. Epub 2015 May 13.

Low neural exosomal levels of cellular survival factors in Alzheimer's disease.

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  • 1Department of Medicine, UCSF Medical Center and the Jewish Home of San Francisco San Francisco, California.
  • 2Memory and Aging Center, Department of Neurology, UCSF Medical Center San Francisco, California.
  • 3Departments of Medicine and Bioengineering, UCSF Medical Center and the Jewish Home of San Francisco San Francisco, California.
  • 4Sanders-Brown Center on Aging, University of Kentucky Lexington, Kentucky.
  • 5Department of Neurology, Mayo Clinic Rochester, Minnesota.
  • 6Intramural Research Program, National Institute on Aging Baltimore, Maryland.


Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.

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