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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Notes/Citation Information

Published in Annals of Clinical and Translational Neurology, v. 2, no. 7, p. 769-773.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Funding Information

Intramural Research Program of the National Institute on Aging (NIA; D. K.), P30 AG028383 (E. L. A.), and an unrestricted grant for method development from Nanosomix, Inc. (E. J. G.).

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Figure S1.

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Table S1.

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Table S2.