ArticleActa neuropathologica communications2018
Brainstem tau pathology in Alzheimer's disease is characterized by increase of three repeat tau and independent of amyloid β.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Experimentally evoked pain in Alzheimer's disease.Journal of the American Association of Nurse Practitioners · 2021Pooled it
- Association between lower body temperature and increased tau pathology in cognitively normal older adults.Neurobiology of disease · 2022Trial
- Connecting HTT intermediate alleles and microRNA dysregulation to enhanced tauopathy in late-onset Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Cellular circadian period and its deviation associate with Alzheimer's pathology and brain aging in cognitively impaired older adults.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Microbiome-Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions.Cells · 2026Review
- Substantia Nigra MRI markers are lower in Alzheimer's disease and are linked to general cognitive function.Brain communications · 2026Article
- Locus coeruleus-entorhinal cortex tract integrity is linked to plasma tau and glial fibrillary acidic protein.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Automated MRI Segmentation of Brainstem Nuclei Critical to Consciousness.Human brain mapping · 2025Observational
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- Spatial differences in gene expression across the dorsal raphe nucleus in a model of early Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Oxidative Stress Triggers a Pivotal Peptide Linked to Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Unveiling a novel memory center in human brain: neurochemical identification of the nucleus incertus, a key pontine locus implicated in stress and neuropathology.Biological research · 2024Article
- Advanced Immunolabeling Method for Optical Volumetric Imaging Reveals Dystrophic Neurites of Dopaminergic Neurons in Alzheimer's Disease Mouse Brain.Molecular neurobiology · 2024Article
- Evidence for a novel neuronal mechanism driving Alzheimer's disease, upstream of amyloid.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Rodent Models of Alzheimer's Disease: Past Misconceptions and Future Prospects.International journal of molecular sciences · 2024Review
- Chronic Sustained Hypoxia Leads to Brainstem Tauopathy and Declines the Power of Rhythms in the Ventrolateral Medulla: Shedding Light on a Possible Mechanism.Molecular neurobiology · 2024Article
- Astrocytic accumulation of tau fibrils isolated from Alzheimer's disease brains induces inflammation, cell-to-cell propagation and neuronal impairment.Acta neuropathologica communications · 2024Article
- Unique Pathology in the Locus Coeruleus of Individuals with Down Syndrome.Journal of Alzheimer's disease : JAD · 2024Article
- Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer's disease.Frontiers in cellular neuroscience · 2024Review
- Oligomeric, phosphorylated, and truncated tau and spliceosome pathology within the entorhinal-hippocampal connectome across stages of Alzheimer's disease.The Journal of comparative neurology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
introductionAlzheimer-type neuropil threads (NTs) and neurofibrillary tangles (NFTs) are comprised of either 4 repeat (4R)-tau, 3 repeat (3R)-tau, or a mixture of both. In the hippocampus, the number of NFTs, and the proportion of 3R tau progressively increases. If this preferential accumulation of 3R tau also occurs in the brainstem, it may be fundamentally related to progression of Alzheimer pathology.
methodsMidbrain and pontine sections of brainstems from 23 cases (Braak-NFT stages I/II: 8, III/IV: 8, and V/VI: 7) were double immunofluorolabeled for 4R and 3R tau. High-resolution (0.645 μm/pixel), in-focus snapshots were tiled to cover entire brain sections using a virtual slide system. Each lesion was classified by size (NT < 200 μm
resultsThe data sets obtained from approximately 286 gigabytes of image files consisted of 847,763 NTs and 7859 NFTs. The proportion of 3R tau-positive NTs and NFTs in the midbrain, and 3R tau-positive NTs in the pons gradually increased with advancing NFT stages, while the proportion of 3R tau-positive NFTs in the pons was already elevated at early stages. Aβ deposits were absent at NFT stages I/II, and when present at later stages, their regional distribution was different from that of tau. These observations suggest that a progressive increase in the proportion of 3R tau occurs independently of Aβ deposits.
conclusionsThis is the first quantitative analysis of NFTs and NTs in the human brainstem. We demonstrate that the proportion of 3R tau in the brainstem neurofibrillary changes increases with disease progression. Because this phenomenon is shared between the brainstem and the hippocampus, this increase may be fundamental to the pathogenesis of Alzheimer disease.
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