APP and myalgic encephalomeyelitis/chronic fatigue syndrome: In conclusion, NE plays a critical role in the LCn loss observed in response to CFS; NE is essential for CFS AEP upregulation and activation in LCn and the formation of toxic APP and tau fragments and the phosphorylation of tau in LCn, and NE is required for CFS activation of AEP in the HC and EC, as measured with AEP-cleaved APP and increased Aβ42 in the HC.