ReviewJournal of Alzheimer's disease : JAD2015
A Unified Hypothesis of Early- and Late-Onset Alzheimer's Disease Pathogenesis.
Review in Journal of Alzheimer's disease : JAD, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Investigation of the myelin-amyloid interplay in Alzheimer's disease: insights from novel dsCMA imaging in mouse and human brains.Acta neuropathologica communications · 2026Article
- Identification and Validation of Biomarkers for Alzheimer's Disease Based on Akt and Wnt Signaling Pathways in Mouse Models.Molecular neurobiology · 2025Article
- Endocrine Dyscrasia in the Etiology and Therapy of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Review
- A biomarker-validated time scale in years of disease progression has identified early- and late-onset subgroups in sporadic Alzheimer's disease.Alzheimer's research & therapy · 2023Article
- Myelin in Alzheimer's disease: culprit or bystander?Acta neuropathologica communications · 2023Review
- Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: A Focus on Insulin Resistance.International journal of molecular sciences · 2023Review
- c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Novel Roles of RNA m6A Methylation Regulators in the Occurrence of Alzheimer's Disease and the Subtype Classification.International journal of molecular sciences · 2022Article
- Immune abnormalities and differential gene expression in the hippocampus and peripheral blood of patients with Alzheimer's disease.Annals of translational medicine · 2022Article
- Rationale, study design and implementation of the LUCINDA Trial: Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer's.Contemporary clinical trials · 2021Article
- Hypogonadism induced by surgical stress and brain trauma is reversed by human chorionic gonadotropin in male rats: A potential therapy for surgical and TBI-induced hypogonadism?Endocrinology, diabetes & metabolism · 2021Article
- Therapeutic B-cell depletion reverses progression of Alzheimer's disease.Nature communications · 2021Article
- The Gαq/phospholipase Cβ signaling system represses tau aggregation.Cellular signalling · 2020Article
- Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases.Biomolecules · 2020Review
- A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer's disease brain.Acta neuropathologica communications · 2019Article
- Adeno-associated virus-based Alzheimer's disease mouse models and potential new therapeutic avenues.British journal of pharmacology · 2019Review
- Mechanisms Associated with Type 2 Diabetes as a Risk Factor for Alzheimer-Related Pathology.Molecular neurobiology · 2019Article
- Article
- Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer's Disease Based on GEO Expression Profile and Its Clinical Significance.BioMed research international · 2019Article
- Innate Immune and Fungal Model of Alzheimer's Disease.Journal of Alzheimer's disease reports · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Early-onset familial Alzheimer's disease (EOFAD) and late-onset sporadic AD (LOSAD) both follow a similar pathological and biochemical course that includes: neuron and synapse loss and dysfunction, microvascular damage, microgliosis, extracellular amyloid-β deposition, tau phosphorylation, formation of intracellular neurofibrillary tangles, endoreduplication and related cell cycle events in affected brain regions. Any mechanistic explanation of AD must accommodate these biochemical and neuropathological features for both forms of the disease. In this insight paper we provide a unifying hypothesis for EOFAD and LOSAD that proposes that the aberrant re-entry of terminally differentiated, post-mitotic neurons into the cell division cycle is a common pathway that explains both early and late-onset forms of AD. Cell cycle abnormalities appear very early in the disease process, prior to the appearance of plaques and tangles, and explain the biochemical (e.g. tau phosphorylation), neuropathological (e.g. neuron hypertrophy; polypoidy) and cognitive changes observed in EOFAD and LOSAD. Genetic mutations in AβPP, PSEN1, and PSEN2 that alter amyloid-β precursor protein and Notch processing drive reactivation of the cell cycle in EOFAD, while age-related reproductive endocrine dyscrasia that upregulates mitogenic TNF signaling and AβPP processing toward the amyloidogenic pathway drives reactivation of the cell cycle in LOSAD. In essence, AβPP and presenilin mutations initiate early, what endocrine dyscrasia initiates later: aberrant cell cycle re-entry of post-mitotic neurons leading to neurodegeneration and cognitive decline in AD. Inhibition of cell cycle re-entry in post-mitotic neurons may be a useful therapeutic strategy to prevent, slow or halt disease progression.
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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.