ReviewMolecular neurodegeneration2025
A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.
Review in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical Practice Recommendations of the Swiss Society for Neuroradiology: Neuroimaging Standards for Enrollment and Disease Monitoring in Anti-Amyloid Immunotherapies.Neuro-degenerative diseases · 2026Guideline
- Cross-disease protein aggregate interactions in neurodegeneration: from molecular mechanisms to therapeutic strategies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Anatomy of a Setback: A Taxonomy of Clinical Trial Failures in Alzheimer's Disease and Strategic Lessons for the Future.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Restoration of Neuronal Metabolism and Memory in Alzheimer's Disease by Reprogramming the Exosomal microRNA Network.Journal of molecular neuroscience : MN · 2026Review
- A single-domain antibody targets aggregation-prone region of α-synuclein to reduce synucleinopathy, rescue neurodegeneration and improve function.bioRxiv : the preprint server for biology · 2026Article
- Tau pSer396 and pSer404 Define Distinct Epitope Regions Linked to Different Antibody Functions.bioRxiv : the preprint server for biology · 2026Article
- APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Dementia etiology classification using NULISA plasma biomarkers and machine learning.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Brain-First vs. Body-First Models in Neurodegenerative Disease: A Perspective Review.NeuroSci · 2026Review
- Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies.Molecular neurobiology · 2026Review
- ZCCHC17: a target for synaptic dysfunction and neuronal excitability in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Neuronal PARIS-STAT3 axis drives tau pathology and glial activation in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Article
- Mitochondria Metabolism Regulates Glucose-Lipid Homeostasis in Neurodegenerative Diseases.Research (Washington, D.C.) · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After decades of disappointment, three disease-modifying therapies for Alzheimer's disease (AD) have been approved since 2021. Burgeoning clinical data on these amyloid β-protein (Aβ) targeting drugs validate the amyloid cascade hypothesis as a molecular roadmap for the development of yet more effective therapeutics and offer a template for drugging other AD-associated aggregation-prone proteins. While there remains much to be learned about the molecular pathology of AD, the current state of knowledge is sufficient to expedite the delivery of new drugs. Mindful of the urgent need of patients, we recommend prioritizing efforts in four directions: finishing the job on Aβ, accelerating and diversifying efforts on tau, and expanding discovery on apolipoprotein E and ⍺-synuclein. For each target, we explain the scientific premise, current efforts, and possible new approaches. In the short- and medium-term, we advocate focusing on the technical innovations required to better drug these already well validated targets. While the focus of this review is on expediating development of monotherapies, the subsequent approval of such agents will enable add-on or combination approaches best suited to individual patients.
Indexed as
Identifiers
What Socratic 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 Socratic graph.