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Updated: Jul 3, 2026
08:16
Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
Published on: June 17, 2015
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Progressive Spread of Beta-amyloid Pathology in an Olfactory-driven Amyloid Precursor Protein Mouse Model
Helen C Murray1, Galit Saar2, Li Bai3
1Department of Anatomy and Medical Imaging and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Auckland 1023, New Zealand; Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Neuroscience
|January 30, 2023
Summary
Alzheimer's disease may start in the nose. This study shows amyloid plaques spread from the olfactory system to the brain in a mouse model, suggesting a new early detection pathway for Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Pathology
- Genetics
Background:
- Alzheimer's disease (AD) is preceded by olfactory dysfunction and amyloid-beta (β-amyloid) plaque accumulation in the olfactory system.
- The olfactory vector hypothesis suggests β-amyloid originates externally and spreads from the olfactory bulb (OB) to other brain regions.
Purpose of the Study:
- To investigate the progressive accumulation and spread of β-amyloid in the brain using a mouse model with humanized mutant amyloid precursor protein (hAPP) expressed in olfactory sensory neurons.
- To determine the role of the olfactory system in the early pathogenesis of AD.
Main Methods:
- Utilized a conditional mouse model overexpressing hAPP in olfactory sensory neurons.
- Employed design-based stereology to quantify β-amyloid plaque burden.
- Used manganese-enhanced MRI to assess olfactory bulb (OB) volume changes.
Main Results:
- Demonstrated progressive accumulation of β-amyloid plaques in the OB and olfactory cortical regions with age.
- Observed reduced OB volumes in mice with early hAPP expression, indicating disrupted development rather than degeneration.
- Showed β-amyloid spread from the olfactory epithelium through the olfactory system to the hippocampus.
Conclusions:
- hAPP expression in the olfactory epithelium drives β-amyloid accumulation and spread via the olfactory system.
- The olfactory system plays a significant role in the early stages of β-amyloid-related AD progression.
- Reduced OB volume in early-onset hAPP models is due to developmental disruption, not neurodegeneration.
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