ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 66 citations in OpenAlex.
- Integrative Multi-Omics Analysis Suggests a Proteostasis-Translation-Neuroimmune Axis Underlying Moxifloxacin Associated Cognitive Impairment.Molecular neurobiology · 2026Article
- Endogenously generated Dutch-type Aβ non-fibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Amyloid precursor protein is a subunit of microglial Hv1 channels.Current opinion in immunology · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Article
- Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions.Cell reports · 2026Article
- Article
- Microglial interferon signaling and Aβ plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.Journal of neuroinflammation · 2025Article
- Human-Mouse Chimeric Brain Models to Study Human Glial-Neuronal and Macroglial-Microglial Interactions.bioRxiv : the preprint server for biology · 2024Article
- Autosomal Dominant Alzheimer's Disease Mutations in Human Microglia Are Not Sufficient to Trigger Amyloid Pathology in WT Mice but Might Affect Pathology in 5XFAD Mice.International journal of molecular sciences · 2024Article
- Rescue of Alzheimer's disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells.Cell reports · 2023Article
- Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts.Frontiers in neurology · 2023Review
- Review
- The clock modulator Nobiletin mitigates astrogliosis-associated neuroinflammation and disease hallmarks in an Alzheimer's disease model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Role of mitophagy in the neurodegenerative diseases and its pharmacological advances: A review.Frontiers in molecular neuroscience · 2022Review
- Microglia activation linking amyloid-β drive tau spatial propagation in Alzheimer's disease.Frontiers in neuroscience · 2022Article
- Modification of Glial Cell Activation through Dendritic Cell Vaccination: Promises for Treatment of Neurodegenerative Diseases.Journal of molecular neuroscience : MN · 2021Review
- Does Diet Have a Role in the Treatment of Alzheimer's Disease?Frontiers in aging neuroscience · 2020Review
- Effects of Probiotic Supplementation on Short Chain Fatty Acids in the AppNL-G-F Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2020Article
Corrections and comments
- Commented on by
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledPrior work suggests that amyloid precursor protein (APP) can function as a proinflammatory receptor on immune cells, such as monocytes and microglia. Therefore, we hypothesized that APP serves this function in microglia during Alzheimer's disease. Although fibrillar amyloid β (Aβ)-stimulated cytokine secretion from both wild-type and APP knock-out (mAPP(-/-)) microglial cultures, oligomeric Aβ was unable to stimulate increased secretion from mAPP(-/-) cells. This was consistent with an ability of oligomeric Aβ to bind APP. Similarly, intracerebroventricular infusions of oligomeric Aβ produced less microgliosis in mAPP(-/-) mice compared with wild-type mice. The mAPP(-/-) mice crossed to an APP/PS1 transgenic mouse line demonstrated reduced microgliosis and cytokine levels and improved memory compared with wild-type mice despite robust fibrillar Aβ plaque deposition. These data define a novel function for microglial APP in regulating their ability to acquire a proinflammatory phenotype during disease. SIGNIFICANCE STATEMENT: A hallmark of Alzheimer's disease (AD) brains is the accumulation of amyloid β (Aβ) peptide within plaques robustly invested with reactive microglia. This supports the notion that Aβ stimulation of microglial activation is one source of brain inflammatory changes during disease. Aβ is a cleavage product of the ubiquitously expressed amyloid precursor protein (APP) and is able to self-associate into a wide variety of differently sized and structurally distinct multimers. In this study, we demonstrate both in vitro and in vivo that nonfibrillar, oligomeric forms of Aβ are able to interact with the parent APP protein to stimulate microglial activation. This provides a mechanism by which metabolism of APP results in possible autocrine or paracrine Aβ production to drive the microgliosis associated with AD brains.
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.