The locus coeruleus (LC) is a small brainstem nucleus that contains the majority of norepinephrine-producing neurons in the central nervous system. These neurons are among the earliest and most severely affected in Alzheimer's disease (AD), showing tau protein pathology even in preclinical stages. [1]
The locus coeruleus is located in the pontine tegmentum and projects widely throughout the brain: [2]
LC neurons release norepinephrine (NE) which modulates: [3]
The locus coeruleus is one of the first sites of tau protein pathology in AD: [4]
Key AD risk genes affecting LC:
LC degeneration contributes to:
LC neurons are critical for arousal:
| Neuron Type | Pathology Onset | Primary Effect |
|---|---|---|
| Locus coeruleus | Earliest (preclinical) | Attention, arousal |
| Basal forebrain cholinergic | Early | Memory |
| Dorsal raphe serotonergic | Moderate | Mood, sleep |
| Substantia nigra dopaminergic | Variable | Motor (PD) |
](/cell-types/microglia-in-alzheimer's---immune-cells-in-ad
--cortical-neurons-in-ad---cortical-involvement
--hippocampal-ca1-neurons---memory-circuits
--basal-forebrain-cholinergic-neurons---cholinergic-loss
###-key-mechanisms
--tau-pathway---tau-pathology
--amyloid-cascade---amyloid-beta-processing
--neuroinflammation---inflammatory-responses
--calcium-dysregulation---calcium-homeostasis
--mitochondrial-dysfunction---energy-metabolism
###-risk-genes
--apoe---major-ad-risk-gene
--trem2---microglial-risk-gene
--app---amyloid-precursor-protein
###-disease-pages
--alzheimer's-disease---main-disease-page
--mild-cognitive-impairment---early-stage)## External Links
Kelly SC, et al. (2017). Locus coeruleus cellular and molecular pathology in Alzheimer's disease. Acta Neuropathologica. 2017. ↩︎
Weinshenker D. (2018). Long road to wear: the locus coeruleus and noradrenergic modulation of cognition. Nature Reviews Neuroscience. 2018. ↩︎
Mravec B, et al. (2014). The locus coeruleus: a crucial neuronal hub in Alzheimer's disease. Journal of Neural Transmission. 2014. ↩︎
Heneka MT, et al. (2015). Locus coeruleus controls Alzheimer's disease pathology by modulating microglial functions. Proceedings of the National Academy of Sciences. 2015. ↩︎