ArticleActa neuropathologica communications2017
Locus coeruleus cellular and molecular pathology during the progression of Alzheimer's disease.
Article in Acta neuropathologica communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers.
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Who cites it
188 citing papers in PubMed, 295 citations in OpenAlex.
- A phase II study repurposing atomoxetine for neuroprotection in mild cognitive impairment.Brain : a journal of neurology · 2022Trial
- Early alteration of the locus coeruleus in phenotypic variants of Alzheimer's disease.Annals of clinical and translational neurology · 2019Trial
- Trial
- Beta 2-adrenergic pathway combats Alzheimer's disease: Restoring cognition and synaptic integrity.Neural regeneration research · 2026Article
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.Molecular psychiatry · 2026Article
- Neuromodulation techniques targeting neurotransmitter dysfunction: Innovation in treatments for Alzheimer's disease.Neural regeneration research · 2026Article
- Locus Coeruleus as a Master Regulator of Diverse Functions in the Central Nervous System: Its Relevance in Ageing and Neurodegenerative Disorders.Annals of neurosciences · 2026Review
- Vulnerability of locus coeruleus connections to aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Locus coeruleus TDP-43 pathology in a community-based cohort: Clinical and pathological correlates.Journal of neuropathology and experimental neurology · 2026Article
- Norepinephrine and dopamine Imbalance in the medial frontal gyrus from patients with Alzheimer's disease.IBRO neuroscience reports · 2026Article
- Shifting focus to preclinical stages: Locus coeruleus tau pathology as a driver and therapeutic target in Alzheimer's disease.Neural regeneration research · 2026Article
- Vulnerability of the locus coeruleus-entorhinal cortex white matter tract in autosomal dominant Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cellular signatures of melanocortin pathway genes across the locus coeruleus.Acta neuropathologica communications · 2026Article
- Photostimulation of locus coeruleus CA1 catecholaminergic terminals reversed Spatial memory impairment in an alzheimer's disease mouse model.Psychopharmacology · 2026Article
- The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.GeroScience · 2026Review
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Decreased Length of Locus Coeruleus Norepinephrine Axons and Increased Amyloid Beta Pathology in Male APP/PS1 Mice During Protracted Abstinence From Alcohol.Neurotoxicity research · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sex and life experience shape locus coeruleus pretangle tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
128 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
A major feature of Alzheimer's disease (AD) is the loss of noradrenergic locus coeruleus (LC) projection neurons that mediate attention, memory, and arousal. However, the extent to which the LC projection system degenerates during the initial stages of AD is still under investigation. To address this question, we performed tyrosine hydroxylase (TH) immunohistochemistry and unbiased stereology of noradrenergic LC neurons in tissue harvested postmortem from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI, a putative prodromal AD stage), or mild/moderate AD. Stereologic estimates of total LC neuron number revealed a 30% loss during the transition from NCI to aMCI, with an additional 25% loss of LC neurons in AD. Decreases in noradrenergic LC neuron number were significantly associated with worsening antemortem global cognitive function as well as poorer performance on neuropsychological tests of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. Reduced LC neuron numbers were also associated with increased postmortem neuropathology. To examine the cellular and molecular pathogenic processes underlying LC neurodegeneration in aMCI, we performed single population microarray analysis. These studies revealed significant reductions in select functional classes of mRNAs regulating mitochondrial respiration, redox homeostasis, and neuritic structural plasticity in neurons accessed from both aMCI and AD subjects compared to NCI. Specific gene expression levels within these functional classes were also associated with global cognitive deterioration and neuropathological burden. Taken together, these observations suggest that noradrenergic LC cellular and molecular pathology is a prominent feature of prodromal disease that contributes to cognitive dysfunction. Moreover, they lend support to a rational basis for targeting LC neuroprotection as a disease modifying strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.