ReviewFrontiers in cellular neuroscience2015
The Maze of APP Processing in Alzheimer's Disease: Where Did We Go Wrong in Reasoning?
Review in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 35 citations in OpenAlex.
- Magnetoreceptive CRY/MagR complexes: linking circadian redox signalling to protein aggregation in Alzheimer's and Parkinson's disease.ADMET & DMPK · 2026Review
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 2025Review
- PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review.Biomedicines · 2024Article
- Pathophysiological Aspects and Therapeutic Armamentarium of Alzheimer's Disease: Recent Trends and Future Development.Cellular and molecular neurobiology · 2023Review
- Endosomal-lysosomal dysfunctions in Alzheimer's disease: Pathogenesis and therapeutic interventions.Metabolic brain disease · 2021Review
- Inflammation Spreading: Negative Spiral Linking Systemic Inflammatory Disorders and Alzheimer's Disease.Frontiers in cellular neuroscience · 2021Article
- The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer's Disease.Frontiers in cellular neuroscience · 2021Review
- A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Molecular mechanisms underlying actions of certain long noncoding RNAs in Alzheimer's disease.Metabolic brain disease · 2020Review
- Medroxyprogesterone Acetate Impairs Amyloid Beta Degradation in a Matrix Metalloproteinase-9 Dependent Manner.Frontiers in aging neuroscience · 2020Article
- Chronic noise exposure exacerbates AD-like neuropathology in SAMP8 mice in relation to Wnt signaling in the PFC and hippocampus.Scientific reports · 2018Article
- ABioMed research international · 2017Review
- Calpain Activation in Alzheimer's Model Mice Is an Artifact of APP and Presenilin Overexpression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Therapies for Prevention and Treatment of Alzheimer's Disease.BioMed research international · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Why has Alzheimer's disease (AD) remained a conundrum today? The main reason is the stagnation in understanding the origins of plaques and tangles. While they are widely thought to be the products of the "aberrant" pathways, we believe that plaques and tangles result from natural aging. From this new perspective, we have proposed that age-related inefficiency of α-secretase is the underpinning for Aβ overproduction. This view contrasts sharply with the current doctrine that Aβ overproduction is the product of the "overactivated" β- and γ-secretases. Following this doctrine, it has been claimed that the two secretases are "positively identified" and that their inhibitors have "successfully reduced Aβ levels." But, why have these studies not led to the understanding of AD or successful clinical trials? And if so, where did they go off course in reasoning? These questions may touch the basics of biological science and must be answered. In this paper, I dissected several prevailing assumptions and some influential reports with an attempt to trace the origins of the conundrum. This work led me to an original model for Aβ overproduction and also to a serious question: given the universal knowledge that boosting α-secretase reduces Aβ, a straightforward highway for intervention, then why is there such an obsession on "inhibiting β- and γ-secretases," a much more costly and twisting road even if possible? This issue requires the attention of policymakers and all researchers. I therefore call for a game change in AD study.
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.