ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Disease-specific neuropathological alterations of the locus coeruleus in Alzheimer's disease, Down syndrome, and Parkinson's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Neuroinflammation and noradrenergic modulation with β2-adrenoceptors: Emerging therapeutic targets for Parkinson's diseases.Neural regeneration research · 2026Article
- The locus coeruleus at the crossroads of inflammation and neurodegeneration in multiple sclerosis.Journal of neuroinflammation · 2026Review
- Deciphering Freezing of Gait: What Neuropathology Reveals About an Episodic Phenomenon.The European journal of neuroscience · 2026Review
- Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimer's dementia.Acta neuropathologica · 2026Article
- Characterizing circadian rest-activity rhythm patterns across Alzheimer's disease continuum in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Use of anti-amyloid-β monoclonal antibodies in persons with Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer's disease, Down syndrome, and Parkinson's disease.NPJ dementia · 2026Article
- Noradrenergic Slow Vasomotion: The Hidden Fluid Pump Linking Sleep, Brain Clearance, and Dementia Pathogenesis.International journal of molecular sciences · 2025Review
- Disease-specific neuropathological alterations of the locus coeruleus in Alzheimer's disease, Down syndrome, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Pharmacologically increasing O-GlcNAcylation increases complexity of astrocytes in the dentate gyrus of TgF344-AD rats.Frontiers in aging neuroscience · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
introductionThe locus coeruleus (LC), the brain's primary source of noradrenaline (NA), undergoes early neurodegeneration in Parkinson's disease (PD), Alzheimer's diseases (AD), and Down syndrome (DS); however, differences have not been examined in parallel.
methodsPost mortem brains (n = 67) from individuals with AD, DS-AD, and PD without and with dementia (PD-D) and controls were analyzed for amyloid beta (Aβ), phosphorylated tau (pTau), α-synuclein, endo-lysosomal alterations, biogenic amines, and selective biomarkers.
resultsLC degeneration correlated with age, peaking in AD and PD-D, while NA and dopaminergic metabolites were significantly reduced only in PD-D. DS-AD, the youngest group, showed the highest Aβ and pTau levels but the least noradrenergic neuron loss. We demonstrated for the first time that endosomal alterations were present in AD, lysosomal changes were present in PD-D/DS-AD, and DYRK1A, a key protein from chromosome 21, was elevated only in DS-AD. DISCUSSION: Loss of noradrenergic neurons may occur independently of amyloid and tau pathologies. HIGHLIGHTS: We provide the first analysis of neuropathological and biochemical features including biogenic amines of the LC in AD, DS, and PD. Loss of noradrenergic neurons was most severe in AD and PD. Only in DS, levels of DYRK1A - a kinase encoded on chromosome 21 and implicated in neurodegenerative processes - were elevated and negatively correlated to biogenic amine levels. Although individuals with DS having AD were the youngest group, they had the highest levels of amyloid and tau pathologies, but less noradrenergic neurons loss compared to other disease groups.
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