ArticleAnnals of neurology2024
Lower Locus Coeruleus Integrity Signals Elevated Entorhinal Tau and Clinical Progression in Asymptomatic Older Individuals.
Article in Annals of neurology, 2024. 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.
- 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
- The monoaminergic systems as drivers of Alzheimer's disease pathophysiology and symptomatology.Current opinion in neurology · 2026Review
- Attenuated pupillary response during visual search in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Atomoxetine Drug Properties for Repurposing as a Candidate Alzheimer's Disease Therapeutic Agent.ACS pharmacology & translational science · 2025Review
- Locus Coeruleus MR Measured Signal Intensity in Fibromyalgia Relative to Healthy Controls.European journal of pain (London, England) · 2025Article
- Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Lower locus coeruleus integrity is associated with diminished practice effects in clinically unimpaired older individuals.Neurobiology of aging · 2025Article
- Locus coeruleus tau validates and informs high-resolution MRI in aging and at earliest Alzheimer's pathology stages.Acta neuropathologica communications · 2025Article
- The locus coeruleus, a blue spot for early diagnosis and prognosis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Noradrenergic therapies in neurodegenerative disease: from symptomatic to disease modifying therapy?Brain communications · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
objectiveElevated entorhinal cortex (EC) tau in low beta-amyloid individuals can predict accumulation of pathology and cognitive decline. We compared the accuracy of magnetic resonance imaging (MRI)-derived locus coeruleus integrity, neocortical beta-amyloid burden by positron emission tomography (PET), and hippocampal volume in identifying elevated entorhinal tau signal in asymptomatic individuals who are considered beta-amyloid PET-negative.
methodsWe included 188 asymptomatic individuals (70.78 ± 11.51 years, 58% female) who underwent 3T-MRI of the locus coeruleus, Pittsburgh compound-B (PiB), and Flortaucipir (FTP) PET. Associations between elevated EC tau and neocortical PiB, hippocampal volume, or locus coeruleus integrity were evaluated and compared using logistic regression and receiver operating characteristic analyses in the PiB- sample with a clinical dementia rating (CDR) of 0. Associations with clinical progression (CDR-sum-of-boxes) over a time span of 6 years were evaluated with Cox proportional hazard models.
resultsWe identified 26 (21%) individuals with high EC FTP in the CDR = 0/PiB- sample. Locus coeruleus integrity was a significantly more sensitive and specific predictor of elevated EC FTP (area under the curve [AUC] = 85%) compared with PiB (AUC = 77%) or hippocampal volume (AUC = 76%). Based on the Youden-index, locus coeruleus integrity obtained a sensitivity of 77% and 85% specificity. Using the resulting locus coeruleus Youden cut-off, lower locus coeruleus integrity was associated with a two-fold increase in clinical progression, including mild cognitive impairment.
interpretationLocus coeruleus integrity has promise as a low-cost, non-invasive screening instrument to detect early cortical tau deposition and associated clinical progression in asymptomatic, low beta-amyloid individuals. ANN NEUROL 2024;96:650-661.
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