ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2021
Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease.
Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 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
202 citing papers in PubMed, 342 citations in OpenAlex.
- A phase 2 randomized, placebo-controlled study on the efficacy and safety of AR1001, a phosphodiesterase-5 inhibitor, in patients with mild-to-moderate Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Trial
- Herpes simplex virus and kallikrein-related peptidases - a functional connection in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Review
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Prion-like transmission and propagation of human β-amyloid to the bank vole rodent model.Acta neuropathologica · 2026Article
- Epigenetic Regulations by Olive Bioactives: Targeting HDAC for Disease Prevention and Therapy.Current nutrition reports · 2026Review
- Investigation of the myelin-amyloid interplay in Alzheimer's disease: insights from novel dsCMA imaging in mouse and human brains.Acta neuropathologica communications · 2026Article
- APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
- Identifying candidate gut microbiota indicators for Alzheimer's disease through integrated data.mSystems · 2026Article
- Intracerebroventricular streptozotocin-induced animal model of Alzheimer's disease: revealing dose optimization, administration regimen, and molecular pathways.Laboratory animal research · 2026Review
- Bridging the gaps in alzheimer's disease: a comprehensive review of current and emerging therapies.Inflammopharmacology · 2026Review
- The microtubule nexus linking amyloid beta and tau: A simple and unifying theory for the underlying cause of Alzheimer's disease.PNAS nexus · 2026Article
- A review of evidence supporting amyloid beta reduction as a surrogate endpoint in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2026Review
- Amyloid-β and Tau in Alzheimer's disease: pathogenesis, mechanisms, and interplay.Cell death & disease · 2026Review
- Innovative Approaches to Alzheimer's Treatment: Utilizing Tacrine Hybrids to Inhibit Amyloid Beta Aggregation as a Strategic Focus.Mini reviews in medicinal chemistry · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Intervention of ginseng-derived macromolecular drugs in Alzheimer's disease: exploring mechanisms and assessing potential.Frontiers in aging neuroscience · 2026Review
- Low-Dimensional Nanomaterials in Alzheimer's Disease: Current Applications.Current Alzheimer research · 2026Review
- Older adults with constipation and Parkinson's disease share comparable gut microbiota.Frontiers in cellular and infection microbiology · 2026Article
142 more citing papers are in PubMed but not listed here.
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 3 institutions in 2 countries.
Funding
Abstract
The etiology of the common, sporadic form of Alzheimer's disease (sAD) is unknown. We hypothesize that tau pathology within select projection neurons with susceptible microenvironments can initiate sAD. This postulate rests on extensive data demonstrating that in human brains tau pathology appears about a decade before the formation of Aβ plaques (Aβps), especially targeting glutamate projection neurons in the association cortex. Data from aging rhesus monkeys show abnormal tau phosphorylation within vulnerable neurons, associated with calcium dysregulation. Abnormally phosphorylated tau (pTau) on microtubules traps APP-containing endosomes, which can increase Aβ production. As Aβ oligomers increase abnormal phosphorylation of tau, this would drive vicious cycles leading to sAD pathology over a long lifespan, with genetic and environmental factors that may accelerate pathological events. This hypothesis could be testable in the aged monkey association cortex that naturally expresses characteristics capable of promoting and sustaining abnormal tau phosphorylation and Aβ production.
Indexed as
Identifiers
What OpenQuestion holds
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.