ArticleJournal of Alzheimer's disease : JAD2019
Locus Coeruleus Degeneration Induces Forebrain Vascular Pathology in a Transgenic Rat Model of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- A phase II study repurposing atomoxetine for neuroprotection in mild cognitive impairment.Brain : a journal of neurology · 2022Trial
- 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
- 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
- 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-dependent locus coeruleus vulnerability in Alzheimer's disease: gut dysbiosis as a driver and probiotic intervention as rescue.Biology of sex differences · 2026Review
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.bioRxiv : the preprint server for biology · 2025Article
- Neuronal gene profiling of tau oligomer-bearing cholinergic nucleus basalis neurons during the onset of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- High-fat feeding has sex-dependent effects on the structure and biomechanical properties of cerebral parenchymal arterioles and cognitive function.American journal of physiology. Heart and circulatory physiology · 2025Article
- Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults.Neurobiology of aging · 2025Article
- Targeting early tau pathology: probiotic diet enhances cognitive function and reduces inflammation in a preclinical Alzheimer's model.Alzheimer's research & therapy · 2025Article
- Noradrenergic therapies in neurodegenerative disease: from symptomatic to disease modifying therapy?Brain communications · 2025Review
- Probiotic supplementation prevents stress-impaired spatial learning and enhances the effects of environmental enrichment.Frontiers in microbiomes · 2025Article
- Novel inductively coupled ear-bars (ICEs) to enhance restored fMRI signal from susceptibility compensation in rats.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.Handbook of experimental pharmacology · 2024Review
- Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Repeated Methamphetamine Administration Results in Axon Loss Prior to Somatic Loss of Substantia Nigra Pars Compacta and Locus Coeruleus Neurons in Male but Not Female Mice.International journal of molecular sciences · 2023Article
- Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Locus coeruleus ablation in mice: protocol optimization, stereology and behavioral impact.Frontiers in cellular neuroscience · 2023Article
- Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels.Molecular neurodegeneration · 2022Article
- The connections of Locus Coeruleus with hypothalamus: potential involvement in Alzheimer's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Noradrenergic locus coeruleus (LC) neuron loss is a significant feature of mild cognitive impairment and Alzheimer's disease (AD). The LC is the primary source of norepinephrine in the forebrain, where it modulates attention and memory in vulnerable cognitive regions such as prefrontal cortex (PFC) and hippocampus. Furthermore, LC-mediated norepinephrine signaling is thought to play a role in blood-brain barrier (BBB) maintenance and neurovascular coupling, suggesting that LC degeneration may impact the high comorbidity of cerebrovascular disease and AD. However, the extent to which LC projection system degeneration influences vascular pathology is not fully understood. To address this question in vivo, we stereotactically lesioned LC projection neurons innervating the PFC of six-month-old Tg344-19 AD rats using the noradrenergic immunotoxin, dopamine-β-hydroxylase IgG-saporin (DBH-sap), or an untargeted control IgG-saporin (IgG-sap). DBH-sap-lesioned animals performed significantly worse than IgG-sap animals on the Barnes maze task in measures of both spatial and working memory. DBH-sap-lesioned rats also displayed increased amyloid and inflammation pathology compared to IgG-sap controls. However, we also discovered prominent parenchymal albumin extravasation with DBH-sap lesions indicative of BBB breakdown. Moreover, microvessel wall-to-lumen ratios were increased in the PFC of DBH-sap compared to IgG-sap rats, suggesting that LC deafferentation results in vascular remodeling. Finally, we noted an early emergence of amyloid angiopathy in the DBH-sap-lesioned Tg344-19 AD rats. Taken together, these data indicate that LC projection system degeneration is a nexus lesion that compromises both vascular and neuronal function in cognitive brain areas during the prodromal stages of AD.
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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 Socratic graph.