ArticleMolecular neurodegeneration2013
Neuron loss in the 5XFAD mouse model of Alzheimer's disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation.
Article in Molecular neurodegeneration, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 274 papers.
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Who cites it
274 citing papers in PubMed, 403 citations in OpenAlex.
- Article
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- Investigation of the myelin-amyloid interplay in Alzheimer's disease: insights from novel dsCMA imaging in mouse and human brains.Acta neuropathologica communications · 2026Article
- Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.Nature aging · 2026Article
- The Central Role of Neuronal Cell Death in Alzheimer's Disease Pathobiology.Biomedicines · 2026Review
- Baicalein alleviates Alzheimer's disease pathology in AD models by activating the PI3K/AKT/GSK3β pathway to inhibit neuronal apoptosis.Scientific reports · 2026Article
- Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.Nature neuroscience · 2026Article
- Non-invasive ovulation tracking enables genetic engineering in wild rodents.Cell reports methods · 2026Article
- Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop.Science advances · 2026Article
- Decoding Alzheimer's Disease One Cell Class at a Time.Cellular and molecular neurobiology · 2026Review
- Functional border-associated macrophages limit Alzheimer's Disease progression.bioRxiv : the preprint server for biology · 2026Article
- Morpho-Functional Characterization and miRNA Profiling of the Retina in the 5xFAD Murine Model of Alzheimer's Disease.Investigative ophthalmology & visual science · 2026Article
- An Acebuche Oil-Enriched Diet Prevents Early-Stage Cerebrovascular Alterations in the 5xFAD Mouse Model of Alzheimer's Disease.Nutrients · 2026Article
- Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop.bioRxiv : the preprint server for biology · 2026Article
- Pre-plaque glutamatergic hyperexcitability, mitochondrial dysfunction, and dendritic remodeling in the hippocampus of one-month-old 5xFAD mice.Frontiers in aging neuroscience · 2026Article
214 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlthough the mechanism of neuron loss in Alzheimer's disease (AD) is enigmatic, it is associated with cerebral accumulation of Aβ42. The 5XFAD mouse model of amyloid deposition expresses five familial AD (FAD) mutations that are additive in driving Aβ42 overproduction. 5XFAD mice exhibit intraneuronal Aβ42 accumulation at 1.5 months, amyloid deposition at 2 months, and memory deficits by 4 months of age.
resultsHere, we demonstrate by unbiased stereology that statistically significant neuron loss occurs by 9 months of age in 5XFAD mice. We validated two Aβ42-selective antibodies by immunostaining 5XFAD; BACE1-/- bigenic brain sections and then used these antibodies to show that intraneuronal Aβ42 and amyloid deposition develop in the same regions where neuron loss is observed in 5XFAD brain. In 5XFAD neuronal soma, intraneuronal Aβ42 accumulates in puncta that co-label for Transferrin receptor and LAMP-1, indicating endosomal and lysosomal localization, respectively. In addition, in young 5XFAD brains, we observed activated Caspase-3 in the soma and proximal dendrites of intraneuronal Aβ42-labeled neurons. In older 5XFAD brains, we found activated Caspase-3-positive punctate accumulations that co-localize with the neuronal marker class III β-tubulin, suggesting neuron loss by apoptosis.
conclusionsTogether, our results indicate a temporal sequence of intraneuronal Aβ42 accumulation, Caspase-3 activation, and neuron loss that implies a potential apoptotic mechanism of neuron death in the 5XFAD mouse.
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