ReviewMolecular neurobiology2019
Could Alzheimer's Disease Originate in the Periphery and If So How So?
Review in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Peripheral immune function and Alzheimer's disease: a living systematic review and critical appraisal.Molecular psychiatry · 2024Pooled it
- The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective.Basic & clinical pharmacology & toxicology · 2026Review
- Context dependent role of miR-486 promoting neuroregeneration of primary sensory neurons downstream of interleukin-6 signal transducer.Molecular therapy. Nucleic acids · 2025Article
- Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.Molecular neurobiology · 2025Review
- Mitochondrial Alterations in Alzheimer's Disease: Insight from the 5xFAD Mouse Model.Molecular neurobiology · 2025Article
- Microecologics and Exercise: Targeting the Microbiota-Gut-Brain Axis for Central Nervous System Disease Intervention.Nutrients · 2025Review
- The role of ultrasonic vocalizations in rat laryngological investigations.Physiology & behavior · 2025Review
- Experimental modeling of Alzheimer's disease: Translational lessons from cross-taxon analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Review
- Article
- Anxiety and Depression: Triggers for Cognitive Loss, Alzheimer's Disease, and Neurodegeneration.Current neurovascular research · 2025Article
- Probiotics, gut microbiota, and brain health: Exploring therapeutic pathways.AIMS microbiology · 2025Review
- Identification of Key Genes in Esketamine's Therapeutic Effects on Perioperative Neurocognitive Disorders via Transcriptome Sequencing.Drug design, development and therapy · 2025Article
- Article
- Emerging Roles of Adaptive Immune Response in Alzheimer's Disease.Aging and disease · 2024Review
- Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease.Cellular and molecular neurobiology · 2024Review
- Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.Brain pathology (Zurich, Switzerland) · 2024Review
- Review
- Astrogliosis, neuritic microstructure, and sex effects: GFAP is an indicator of neuritic orientation in women.Brain, behavior, and immunity · 2023Article
- Preserved endothelium-independent vascular function with aging in men and women: evidence from the peripheral and cerebral vasculature.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD. In particular, as a result of increased activity of triggering receptor expressed on myeloid cells 2 (TREM-2), the presence of the apolipoprotein E4 (ApoE4) isoform, and changes in ANK1 expression, with subsequent changes in miR-486 leading to altered levels of protein kinase B (Akt), mechanistic (previously mammalian) target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), all of which play major roles in microglial activation, proliferation and survival, there is activation of microglia, leading to the subsequent (further) production of cytokines, chemokines, nitric oxide, prostaglandins, reactive oxygen species, inducible nitric oxide synthase and cyclooxygenase-2, and other mediators of inflammation and neurotoxicity. These changes are associated with the development of amyloid and tau pathology, mitochondrial dysfunction (including impaired activity of the electron transport chain, depleted basal mitochondrial potential and oxidative damage to key tricarboxylic acid enzymes), synaptic dysfunction, altered glycogen synthase kinase-3 (GSK-3) activity, mTOR activation, impairment of autophagy, compromised ubiquitin-proteasome system, iron dyshomeostasis, changes in APP translation, amyloid plaque formation, tau hyperphosphorylation and neurofibrillary tangle formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.