ReviewMolecular neurobiology2025
Toward a Unified Framework in Molecular Neurobiology of Alzheimer's Disease: Revisiting the Pathophysiological Hypotheses.
Review in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed.
- Long-term risk of dementia following encephalitis: a large-scale retrospective cohort study of electronic health records.Journal of neurology · 2026Article
- Review
- Rodent Models of Alzheimer's Disease: Bridging the Translational Gap Through Systems-Level Integration.Biomedicines · 2026Review
- Neuroprotective Potential of Nardostachys jatamansi Extract via Keap1-Nrf2 Pathway Regulation in Parkinson's Disease.Applied biochemistry and biotechnology · 2026Article
- Curcumin in Alzheimer's Disease: From Mechanistic Insights to Translational Challenges and Emerging Curcuminoid Strategies.International journal of molecular sciences · 2026Review
- IL-4 in Alzheimer's Disease-Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Unlocking the aging brain: mTORC1 as a convergent integrator for neurodegeneration and therapeutic intervention.Biogerontology · 2026Review
- Targeting the gut-brain axis: microbial interventions for neurological disorders.Metabolic brain disease · 2026Review
- From Molecular Networks to Medicines: Targeting Complexity in Alzheimer's Disease (AD) Therapy.Molecular neurobiology · 2026Review
- Lysophospholipids in Synucleinopathies: A Conceptual Framework Linking Proteostasis and Neuroinflammatory Signaling.Brain sciences · 2026Review
- Humanized Klotho haplotypes cause widespread transcriptomic changes in mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Oxidative stress as a converging mechanism of aging and neurodegeneration: From molecular pathways to therapeutic targets.Narra J · 2026Review
- Exploring Early Neurodegeneration Through Fasting-Induced Metabolic Signatures and High-Sensitivity Biomarkers.Current issues in molecular biology · 2026Review
- Impact of disease burden on VOBMJ open · 2026Article
- Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders.Neurology international · 2026Review
- Regulon Reconstruction Uncovers Novel Deregulated Factors in Alzheimer's Disease.Molecular neurobiology · 2026Article
- Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation.Neurology international · 2026Review
- Recent Advances in Polyoxometalates Targeting Proteins Associated with Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Applications.International journal of molecular sciences · 2026Review
- Genomic and proteomic conversion of brain ischemia to Alzheimer's disease.Frontiers in cell and developmental biology · 2026Review
- Alzheimer's disease: A comprehensive review of epidemiology, pathophysiology, diagnosis, and treatment.AIMS neuroscience · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite decades of research, Alzheimer's disease (AD) remains without a curative therapy. While amyloid- and tau-centered approaches have dominated the field, failures of monotherapeutic strategies underscore the need for a broader system-level understanding. Here, this review critically revisits the principal hypotheses of AD pathogenesis, including the amyloid cascade, tauopathy, neuroinflammation, cholinergic dysfunction, oxidative and mitochondrial stress, metal dyshomeostasis, autophagy-lysosomal failure, genetic susceptibility, and infectious triggers. This review synthesizes molecular and cellular evidence from human genetics, neuropathology, and experimental models, correcting common misconceptions and emphasizing interactions between pathways. Neuroinflammation is increasingly recognized as a central hub linking amyloid, tau, and vascular factors, while mitochondrial and lysosomal dysfunctions emerge as amplifiers of proteotoxic stress. Genetic studies highlight apolipoprotein-E ε4 (APOE ε4) as the strongest common risk allele, but also implicate genes involved in endosomal trafficking, lipid metabolism, and immune regulation. Taken together, AD is best understood as a multi-hit disorder in which converging processes, rather than a single driver, dictate disease initiation and progression. This narrative review proposes a systems neurobiology framework that integrates these mechanisms and identifies key points of convergence amenable to therapeutic targeting and biomarker development. Finally, this reappraisal aims to inform future research directions and guide the rational design of multi-target interventions.
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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 Socratic graph.