ArticleAging cell2025
Locus coeruleus vulnerability to tau hyperphosphorylation in a rat model.
Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- 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
- Shifting focus to preclinical stages: Locus coeruleus tau pathology as a driver and therapeutic target in Alzheimer's disease.Neural regeneration research · 2026Article
- Gypenoside XLIX and Mitochondria-Associated ER Membranes in Non-Alcoholic Fatty Liver Disease: Mechanistic Insights and Emerging Perspectives.Molecules (Basel, Switzerland) · 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
- Sex and life experience shape locus coeruleus pretangle tau pathology.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
- Sex-dependent locus coeruleus vulnerability in Alzheimer's disease: gut dysbiosis as a driver and probiotic intervention as rescue.Biology of sex differences · 2026Review
- Noradrenergic Locus Coeruleus-CA3 Activation Alleviates Neuropathic Pain and Anxiety- and Depression-Like Behaviors by Suppressing Microglial Neuroinflammation in SNI Mice.CNS neuroscience & therapeutics · 2025Article
- Article
- The locus coeruleus, a blue spot for early diagnosis and prognosis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
Post-mortem investigations indicate that the locus coeruleus (LC) is the initial site of hyperphosphorylated pretangle tau, a precursor to neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD). The presence of pretangle tau and NFTs correlates with AD progression and symptomatology. LC neuron integrity and quantity are linked to cognitive performance, with degeneration strongly associated with AD. Despite their importance, the mechanisms of pretangle tau-induced LC degeneration are unclear. This study examined the transcriptomic and mitochondrial profiles of LC noradrenergic neurons after transduction with pseudophosphorylated human tau. Tau hyperphosphorylation increased the somatic expression of the L-type calcium channel (LTCC), impaired mitochondrial health, and led to deficits in spatial and olfactory learning. Sex-dependent alterations in gene expression were observed in rats transduced with pretangle tau. Chronic LTCC blockade prevented behavioral deficits and altered mitochondrial mRNA expression, suggesting a potential link between LTCC hyperactivity and mitochondrial dysfunction. Our research provides insights into the consequences of tau pathology in the originating structure of AD.
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Registered trials
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