ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Olfactory-Cleft Biopsy in Alzheimer's Disease: An Emerging Neuroimmune Window into Preclinical Pathobiology.International journal of molecular sciences · 2026Review
- Up regulated hippocampal insulin pathway and oxidative stress are related to opposite changes in olfaction and episodic memory in a compensatory metabolic syndrome model in rats.Frontiers in cellular neuroscience · 2026Article
- Cholinergic-like neurons and cerebral spheroids bearing the PSEN1 p.Ile416Thr variant mirror Alzheimer's disease neuropathology.Scientific reports · 2023Article
- Progressive Spread of Beta-amyloid Pathology in an Olfactory-driven Amyloid Precursor Protein Mouse Model.Neuroscience · 2023Article
- Human APOE ɛ3 and APOE ɛ4 Alleles Have Differential Effects on Mouse Olfactory Epithelium.Journal of Alzheimer's disease : JAD · 2022Article
- Olfactory neuropathology in Alzheimer's disease: a sign of ongoing neurodegeneration.BMB reports · 2021Review
- Alterations in odor hedonics in the 5XFAD Alzheimer's disease mouse model and the influence of sex.Behavioral neuroscience · 2020Article
- Alzheimer's Disease: What Can We Learn From the Peripheral Olfactory System?Frontiers in neuroscience · 2020Review
- Article
- "Till Death Do Us Part": A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb.Frontiers in neuroscience · 2018Review
- The olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases.Neurobiology of disease · 2018Article
- Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of β-amyloid oligomer.Cell death & disease · 2017Article
- Disruption of visual circuit formation and refinement in a mouse model of autism.Autism research : official journal of the International Society for Autism Research · 2017Article
- Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model.NeuroImage · 2015Article
- Early hyperactivity in lateral entorhinal cortex is associated with elevated levels of AβPP metabolites in the Tg2576 mouse model of Alzheimer's disease.Experimental neurology · 2015Article
- Connectivity of Pathology: The Olfactory System as a Model for Network-Driven Mechanisms of Alzheimer's Disease Pathogenesis.Frontiers in aging neuroscience · 2015Review
- Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer's Disease.Current geriatrics reports · 2014Article
- Biomarkers of Alzheimer's disease risk in peripheral tissues; focus on buccal cells.Current Alzheimer research · 2014Review
- Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Amyloid precursor protein (APP) has long been linked to the neurodegeneration of Alzheimer's disease (AD), but the associated cell death has been difficult to capture in vivo, and the role of APP in effecting neuron loss is still unclear. Olfactory dysfunction is an early symptom of AD with amyloid pathology in the olfactory epithelium correlating well to the brain pathology of AD patients. As olfactory sensory neurons (OSNs) regenerate continuously with immature and mature OSNs coexisting in the same olfactory epithelium, we sought to use this unique system to study APP-induced neurodegeneration. Here we have developed an olfactory-based transgenic mouse model that overexpresses humanized APP containing familial AD mutations (hAPP) in either mature or immature OSNs, and found that despite the absence of extracellular plaques a striking number of apoptotic neurons were detected by 3 weeks of age. Importantly, apoptosis was restricted to the specific population overexpressing hAPP, either mature or immature OSNs, sparing those without hAPP. Interestingly, we observed that this widespread neurodegeneration could be rapidly rescued by reducing hAPP expression levels in immature neurons. Together, these data argue that overexpressing hAPP alone could induce cell-autonomous apoptosis in both mature and immature neurons, challenging the notion that amyloid plaques are necessary for neurodegeneration. Furthermore, we show that hAPP-induced neurodegeneration is reversible, suggesting that AD-related neural loss could potentially be rescued. Thus, we propose that this unique in vivo model will not only help determine the mechanisms underlying AD-related neurodegeneration but also serve as a platform to test possible treatments.
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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.