Monitoring protein aggregation and toxicity in Alzheimer's disease mouse models using in vivo imaging
Open accessAbstract
Aggregation of amyloid beta peptide into senile plaques and hyperphosphorylated tau protein into neurofibrillary tangles in the brain are the pathological hallmarks of Alzheimer's disease. Despite over a century of research into these lesions, the exact relationship between pathology and neurotoxicity has yet to be fully elucidated. In order to study the formation of plaques and tangles and their effects on the brain, we have applied multiphoton in vivo imaging of transgenic mouse models of Alzheimer's disease. This technique allows longitudinal imaging of pathological aggregation of proteins and the subsequent changes in surrounding neuropil neurodegeneration and recovery after therapeutic interventions.
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oAβ species accumulate at the periphery of dense-cored plaques and compact plaques enhance Aβ toxicity indirectly by creating a platform on which toxic oAβ species can accumulate or stabilize.
“A renewed interest in the pathological role of plaques has suggested that oA species accumulate at the periphery of densecored plaques (60,61) and that compact plaques enhance A toxicity indirectly by creating a platform on which toxic oA species can accumulate or stabilize.”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [61]
The Discussion (page unavailable) links plaques to nearby neuronal damage and identifies soluble Aβ as a possible mediator. It does not say that oligomeric Aβ accumulates at the periphery of dense-cored plaques or that compact plaques provide a platform that stabilizes it. Searches for oligomers at plaque edges and for the proposed platform mechanism found no passage addressing those points. (LLM, conf=0.70)
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- Authors
- Spires-Jones, T. L., Calignon, A. D., Meyer-Luehmann, M., Bacskai, B. J., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Venue
- Methods
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 53
- Issue
- 3
- Pages
- 201-207
- ISSN
- 1046-2023 (ISSN-L)
- PMC
- PMC3049845
- OpenAlex
- W2092395722
- Cited by
- 24
- References
- 44
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- NIH (AG08487, K99AG33670, EB000768, AG026249)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta aggregation, amyloid plaques, tau hyperphosphorylation, neurofibrillary tangles, neurodegeneration, in vivo imaging, multiphoton microscopy, transgenic mouse model, longitudinal imaging
- MeSH terms
- Alzheimer Disease, Amyloid, Anesthesia, Animals, Brain, Craniotomy, Disease Models, Animal, Genetic Vectors, Humans, Image Processing, Computer-Assisted, Neurofibrillary Tangles, Microscopy, Fluorescence, Multiphoton, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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