ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The correlation between olfactory bulb volume and T&T odor threshold: a systematic review and meta-analysis.Brain imaging and behavior · 2026Pooled it
- Olfactory Evoked Potentials and Brain MRI Outcomes in Multiple Sclerosis Patients: A Cross-Sectional Study.Journal of clinical medicine · 2024Article
- Aging-associated sensory decline and Alzheimer's disease.Molecular neurodegeneration · 2024Review
- Amelioration of Cognitive and Olfactory System Deficits in APOE4 Transgenic Mice with DHA Treatment.Molecular neurobiology · 2023Article
- Progressive Spread of Beta-amyloid Pathology in an Olfactory-driven Amyloid Precursor Protein Mouse Model.Neuroscience · 2023Article
- Adult neurogenesis alters response to an aversive distractor in a labyrinth maze without affecting spatial learning or memory.Hippocampus · 2021Article
- Precocious myelination in a mouse model of autism.Translational psychiatry · 2019Article
- "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
- 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
- DNA polymerase β decrement triggers death of olfactory bulb cells and impairs olfaction in a mouse model of Alzheimer's disease.Aging cell · 2017Article
- Dendritic overgrowth and elevated ERK signaling during neonatal development in a mouse model of autism.PloS one · 2017Article
- Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography.Alzheimer's & dementia (Amsterdam, Netherlands) · 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
- At the interface of sensory and motor dysfunctions and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Review
- The role of olfactory challenge tests in incipient dementia and clinical trial design.Current neurology and neuroscience reports · 2014Review
- Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer's Disease.Current geriatrics reports · 2014Article
- Cortical odor processing in health and disease.Progress in brain research · 2014Review
- Spared piriform cortical single-unit odor processing and odor discrimination in the Tg2576 mouse model of Alzheimer's disease.PloS one · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Neural circuits maintain a precise organization that is vital for normal brain functions and behaviors, but become disrupted during neurological disease. Understanding the connection between wiring accuracy and function to measure disease progression or recovery has been difficult because of the complexity of behavioral circuits. The olfactory system maintains well-defined neural connections that regenerate throughout life. We previously established a reversible in vivo model of Alzheimer's disease by overexpressing a humanized mutated amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs). Using this model, we currently show that hAPP is present in the OSN axons of mutant mice, which exhibit strong caspase3 signal and reduced synaptic protein expression by 3 weeks of age. In the olfactory bulb, we show that glomerular structure is distorted and OSN axonal convergence is lost. In vivo functional imaging experiments further demonstrate disruption of the glomerular circuitry, and behavioral assays reveal that olfactory function is significantly impaired. Because OSNs regenerate, we also tested if the system could recover from hAPP-induced disruption. We found that after 1 or 3 weeks of shutting-off hAPP expression, the glomerular circuit was partially restored both anatomically and functionally, with behavioral deficits similarly reversed. Interestingly, the degree of functional recovery tracked directly with circuit restoration. Together, these data demonstrate that hAPP-induced circuit disruption and subsequent recovery can occur rapidly and that behavior can provide a measure of circuit organization. Thus, olfaction may serve as a useful biomarker to both follow disease progression and gauge potential recovery.
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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.