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Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance - PubMed

7 hours ago
  • #Alzheimer's disease
  • #sleep regulation
  • #glymphatic clearance
  • Neuromodulatory subcortical systems (NSS) regulate arousal, cognition, and sleep-wake transitions.
  • Dysfunction of NSS is linked to Alzheimer's disease (AD) pathogenesis, occurring in the preclinical phase.
  • NSS degeneration affects sleep and impairs glymphatic clearance, which removes amyloid beta and neurotoxic proteins.
  • Wake-promoting neuromodulators like norepinephrine, histamine, and orexin influence AD pathology, sleep regulation, and brain fluid dynamics.
  • NSS dysfunction may create a cycle of disrupted sleep, impaired clearance, and neurodegeneration, highlighting the need for pharmacological interventions.