ReviewLaboratory investigation; a journal of technical methods and pathology2019
The amyloid cascade and Alzheimer's disease therapeutics: theory versus observation.
Review in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 116 citations in OpenAlex.
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- Analysis of amyloid beta oligomers by cyclic ion mobility-mass spectrometry.Analytical and bioanalytical chemistry · 2026Article
- The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease.Journal of internal medicine · 2026Review
- Bloodwork-free Early Screening for Alzheimer's Disease via Comorbid Pattern Recognition in Electronic Health Records.Research square · 2026Article
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Targeting Various Pathogenic Pathways for the Development of Anti-alzheimer's Drugs: An Update.Current topics in medicinal chemistry · 2025Review
- Are current etiological theories of Alzheimer's disease falsifiable? An epistemological assessment.Frontiers in aging neuroscience · 2025Article
- Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.Current Alzheimer research · 2025Review
- Isotschimgine promotes lifespan, healthspan and neuroprotection of Caenorhabditis elegans via the activation of nuclear hormone receptors.Biogerontology · 2024Article
- Central role of brain regulatory T cells in the inflammatory cascade in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CoVAMPnet: Comparative Markov State Analysis for Studying Effects of Drug Candidates on Disordered Biomolecules.JACS Au · 2024Article
- Data-driven Stochastic Model for Quantifying the Interplay Between Amyloid-beta and Calcium Levels in Alzheimer's Disease.Statistical analysis and data mining · 2024Article
- A Scoping Review of Alzheimers Disease Hypotheses: An Array of Uni- and Multi-Factorial Theories.Journal of Alzheimer's disease : JAD · 2024Article
- In 2024, theFrontiers in aging neuroscience · 2024Article
- PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Therapeutic Potential of P110 Peptide: New Insights into Treatment of Alzheimer's Disease.Life (Basel, Switzerland) · 2023Article
- Effects of Redox Homeostasis and Mitochondrial Damage on Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Disrupting Dimeric β-Amyloid by Electric Fields.ACS physical chemistry Au · 2023Article
1 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
The identification of amyloid-β precursor protein (APP) pathogenic mutations in familial early onset Alzheimer's disease (AD), along with knowledge that amyloid-β (Aβ) was the principle protein component of senile plaques, led to the establishment of the amyloid cascade hypothesis. Down syndrome substantiated the hypothesis, given an extra copy of the APP gene and invariable AD pathology hallmarks that occur by middle age. An abundance of support for the amyloid cascade hypothesis followed. Prion-like protein misfolding and non-Mendelian transmission of neurotoxicity are among recent areas of investigation. Aβ-targeted clinical trials have been disappointing, with negative results attributed to inadequacies in patient selection, challenges in pharmacology, and incomplete knowledge of the most appropriate target. There is evidence, however, that proof of concept has been achieved, i.e., clearance of Aβ during life, but with no significant changes in cognitive trajectory in AD. Whether the time, effort, and expense of Aβ-targeted therapy will prove valuable will be determined over time, as Aβ-centered clinical trials continue to dominate therapeutic strategies. It seems reasonable to hypothesize that the amyloid cascade is intimately involved in AD, in parallel with disease pathogenesis, but that removal of toxic Aβ is insufficient for an effective disease modification.
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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.