ArticleBiological psychiatry2013
Selective loss of noradrenaline exacerbates early cognitive dysfunction and synaptic deficits in APP/PS1 mice.
Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Bibliometric analysis: Research trends of acupuncture treatment to cognitive impairment in recent 15 years.Frontiers in psychology · 2022Pooled it
- 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
- Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Sex-dependent locus coeruleus vulnerability in Alzheimer's disease: gut dysbiosis as a driver and probiotic intervention as rescue.Biology of sex differences · 2026Review
- Article
- Reboxetine Treatment Reduces Hippocampal Gliosis in the P301S Tauopathy Mouse Model.ASN neuro · 2026Article
- Synergetic effect of a DSP4-induced locus coeruleus lesion and systemic LPS exacerbates substantia nigra dopaminergic neuron loss.Scientific reports · 2025Article
- αPharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Noradrenergic signaling controls Alzheimer's disease pathology via activation of microglial β2 adrenergic receptors.Brain, behavior, and immunity · 2025Article
- Impact of noradrenergic inhibition on neuroinflammation and pathophysiology in mouse models of Alzheimer's disease.Journal of neuroinflammation · 2024Article
- Light-exercise-induced dopaminergic and noradrenergic stimulation in the dorsal hippocampus: Using a rat physiological exercise model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Microglia heterogeneity in health and disease.FEBS open bio · 2024Review
- Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.Handbook of experimental pharmacology · 2024Review
- Locus Coeruleus Dysfunction and Trigeminal Mesencephalic Nucleus Degeneration: A Cue for Periodontal Infection Mediated Damage in Alzheimer's Disease?International journal of environmental research and public health · 2023Review
- Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer's disease mouse model.Frontiers in cellular neuroscience · 2023Article
- The Contribution of the Locus Coeruleus-Noradrenaline System Degeneration during the Progression of Alzheimer's Disease.Biology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDegeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs early and is ubiquitous in Alzheimer's disease (AD). Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive deficits in several transgenic mouse models of AD. Because the LC contains multiple neuromodulators known to affect amyloid β toxicity and cognitive function, the specific role of noradrenaline (NA) in AD is not well understood.
methodsTo determine the consequences of selective NA deficiency in an AD mouse model, we crossed dopamine β-hydroxylase (DBH) knockout mice with amyloid precursor protein (APP)/presenilin-1 (PS1) mice overexpressing mutant APP and PS1. Dopamine β-hydroxylase (-/-) mice are unable to synthesize NA but otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal long-term potentiation, and synaptic protein levels were assessed.
resultsThe modest impairments in spatial memory and hippocampal long-term potentiation displayed by young APP/PS1 or DBH (-/-) single mutant mice were augmented in DBH (-/-)/APP/PS1 double mutant mice. Deficits were associated with reduced levels of total calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptor 2A and increased N-methyl-D-aspartate receptor 2B levels and were independent of amyloid β accumulation. Spatial memory performance was partly improved by treatment with the NA precursor drug L-threo-dihydroxyphenylserine.
conclusionsThese results indicate that early LC degeneration and subsequent NA deficiency in AD may contribute to cognitive deficits via altered levels of calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptors and suggest that NA supplementation could be beneficial in early AD.
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