Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer\u27s 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\u27s disease patients than controls (P \u3c 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\u27s disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer\u27s disease neurotoxic proteins
