ArticleScience translational medicine2021
In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer's disease pathology and cognitive decline.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed.
- Altered locus coeruleus links to atrophy and hypometabolism in individuals with high Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Trial
- Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults in a randomized clinical trial.International journal of psychophysiology : official journal of the International Organization of Psychophysiology · 2023Trial
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Are infraslow oscillations the missing link between sleep and Alzheimer's?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Astrocyte reactivity modifies the effects of locus coeruleus norepinephrine-related dysfunction on tau and its impact on cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- 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
- A gradual and sustainable approach to diagnosing sleep and circadian disturbances in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Acupuncture-induced changes in locus coeruleus connectivity and memory improvement in patients with amnestic cognitive impairment.IBRO neuroscience reports · 2026Article
- The Pupil-Brain System at Rest: Spontaneous Pupil Fluctuations as Markers of Neuromodulatory and Network Dynamics.Psychophysiology · 2026Review
- Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimer's dementia.Acta neuropathologica · 2026Article
- Neuroinflammation and Senescence Are Detected in Brainstems of Mice Latently Infected with HSV-1.Pathogens (Basel, Switzerland) · 2026Article
- Article
- Stereological Assessment of Locus Coeruleus in the Mouse: A Methodological Study in Pups and Adult Animals.Methods and protocols · 2026Article
- Attenuated pupillary response during visual search in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- 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
- Pain Modulation and Central Sensitization in Painful Diabetic Peripheral Neuropathy: Updated Narrative Review and Future Directions.Journal of diabetes · 2026Review
- The monoaminergic systems as drivers of Alzheimer's disease pathophysiology and symptomatology.Current opinion in neurology · 2026Review
- Locus coeruleus degeneration is associated with cortical tau deposition and cognitive decline in older adults at familial risk of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Several autopsy studies recognize the locus coeruleus (LC) as the initial site of hyperphosphorylated TAU aggregation, and as the number of LC neurons harboring TAU increases, TAU pathology emerges throughout the cortex. By conjointly using dedicated MRI measures of LC integrity and TAU and amyloid PET imaging, we aimed to address the question whether in vivo LC measures relate to initial cortical patterns of Alzheimer’s disease (AD) fibrillar proteinopathies or cognitive dysfunction in 174 cognitively unimpaired and impaired older individuals with longitudinal cognitive measures. To guide our interpretations, we verified these associations in autopsy data from 1524 Religious Orders Study and Rush Memory and Aging Project and 2145 National Alzheimer’s Coordinating Center cases providing three different LC measures (pigmentation, tangle density, and neuronal density), Braak staging, β-amyloid, and longitudinal cognitive measures. Lower LC integrity was associated with elevated TAU deposition in the entorhinal cortex among unimpaired individuals consistent with postmortem correlations between LC tangle density and successive Braak staging. LC pigmentation ratings correlated with LC neuronal density but not with LC tangle density and were particularly worse at advanced Braak stages. In the context of elevated β-amyloid, lower LC integrity and greater cortical tangle density were associated with greater TAU burden beyond the medial temporal lobe and retrospective memory decline. These findings support neuropathologic data in which early LC TAU accumulation relates to disease progression and identify LC integrity as a promising indicator of initial AD-related processes and subtle changes in cognitive trajectories of preclinical AD.
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