ArticleJournal of Alzheimer's disease : JAD2022
Consequences of Hyperphosphorylated Tau in the Locus Coeruleus on Behavior and Cognition in a Rat Model of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2022. 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, 41 citations in OpenAlex.
- A new hope: locus coeruleus-norepinephrine system at the nexus of neuropsychiatric symptoms.Molecular psychiatry · 2026Review
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.Molecular psychiatry · 2026Article
- Hypothalamus Amyloid Levels Are Associated with Early Sex-Dependent Alterations in Peripheral Energy Homeostasis in TgF344-AD Rats.Molecular neurobiology · 2026Article
- Signaling Pathways Triggering Therapeutical Potential of Marine-Derived Polysaccharides in Alzheimer's Disease: A Recent Review.Molecular neurobiology · 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
- 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
- Spatial pattern separation deficits in early Alzheimer's disease are comparable in humans and animal models.Scientific reports · 2026Article
- Lipidomic fingerprints reveal sex-, age-, and disease-dependent differences in the TgF344-AD transgenic rats.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.bioRxiv : the preprint server for biology · 2025Article
- Diversity-sensitive brain clocks linked to biophysical mechanisms in aging and dementia.Nature. Mental health · 2025Article
- Protective effects of polydatin amphiphilic chitosan nanocarriers against an aluminum chloride-induced model of Alzheimer's disease in rats: relevance to its anti-inflammatory and antioxidant effects.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus.bioRxiv : the preprint server for biology · 2025Article
- Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Early emergence of motivational and hedonic feeding deficits in the TgF344-AD rat model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- The locus coeruleus, a blue spot for early diagnosis and prognosis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Examining resilience to Alzheimer's disease through the lens of monoaminergic neuromodulator systems.Trends in neurosciences · 2024Review
- Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.bioRxiv : the preprint server for biology · 2024Article
- Article
- In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat.Brain, behavior, & immunity - health · 2024Article
- Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer's disease.Alzheimer's research & therapy · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
backgroundThe locus coeruleus (LC) is one of the earliest brain regions to accumulate hyperphosphorylated tau, but a lack of animal models that recapitulate this pathology has hampered our understanding of its contributions to Alzheimer's disease (AD) pathophysiology.
objectiveWe previously reported that TgF344-AD rats, which overexpress mutant human amyloid precursor protein and presenilin-1, accumulate early endogenous hyperphosphorylated tau in the LC. Here, we used TgF344-AD rats and a wild-type (WT) human tau virus to interrogate the effects of endogenous hyperphosphorylated rat tau and human tau in the LC on AD-related neuropathology and behavior.
methodsTwo-month-old TgF344-AD and WT rats received bilateral LC infusions of full-length WT human tau or mCherry control virus driven by the noradrenergic-specific PRSx8 promoter. Rats were subsequently assessed at 6 and 12 months for arousal (sleep latency), anxiety-like behavior (open field, elevated plus maze, novelty-suppressed feeding), passive coping (forced swim task), and learning and memory (Morris water maze and fear conditioning). Hippocampal microglia, astrocyte, and AD pathology were evaluated using immunohistochemistry.
resultsIn general, the effects of age were more pronounced than genotype or treatment; older rats displayed greater hippocampal pathology, took longer to fall asleep, had reduced locomotor activity, floated more, and had impaired cognition compared to younger animals. TgF344-AD rats showed increased anxiety-like behavior and impaired learning and memory. The tau virus had negligible influence on most measures.
conclusionEffects of hyperphosphorylated tau on AD-like neuropathology and behavioral symptoms were subtle. Further investigation of different forms of tau is warranted.
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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.