Long Road to Ruin: Noradrenergic Dysfunction in Neurodegenerative Disease

Trends Neurosci. 2018 Apr;41(4):211-223. doi: 10.1016/j.tins.2018.01.010. Epub 2018 Feb 20.


It has been known for decades that degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs in both Alzheimer's disease (AD) and Parkinson's disease (PD), but it was given scant attention. It is now recognized that hyperphosphorylated tau in the LC is the first detectable AD-like neuropathology in the human brain, α-synuclein inclusions in the LC represent an early step in PD, and experimental LC lesions exacerbate neuropathology and cognitive/behavioral deficits in animal models. The purpose of this review is to consider the causes and consequences of LC pathology, dysfunction, and degeneration, as well as their implications for early detection and treatment.

Keywords: Alzheimer’s disease; Parkinson’s disease; alpha-synuclein; locus coeruleus; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Animals
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / physiopathology*
  • Humans
  • Locus Coeruleus / physiopathology*
  • Neurons / metabolism
  • Neurons / pathology
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology*
  • alpha-Synuclein / metabolism


  • alpha-Synuclein