Growth arrest of individual senile plaques in a model of Alzheimer's disease observed by in vivo multiphoton microscopy
- PMID: 11157072
- PMCID: PMC6762315
- DOI: 10.1523/JNEUROSCI.21-03-00858.2001
Growth arrest of individual senile plaques in a model of Alzheimer's disease observed by in vivo multiphoton microscopy
Abstract
In Alzheimer's disease, amyloid-beta peptide aggregates in the extracellular space to form senile plaques. The process of plaque deposition and growth has been modeled on the basis of in vitro experiments in ways that lead to divergent predictions: either a diffusion-limited growth model in which plaques grow by first-order kinetics, or a dynamic model of continual deposition and asymmetrical clearance in which plaques reach a stable size and stop growing but evolve morphologically over time. The models have not been tested in vivo because plaques are too small (by several orders of magnitude) for conventional imaging modalities. We now report in vivo multiphoton laser scanning imaging of thioflavine S-stained senile plaques in the Tg2576 transgenic mouse model of Alzheimer's disease to test these biophysical models and show that there is no detectable change in plaque size over extended periods of time. Qualitatively, geometric features remain unchanged over time in the vast majority of the 349 plaques imaged and re-imaged. Intervals as long as 5 months were obtained. Nonetheless, rare examples of growth or shrinkage of individual plaques do occur, and new plaques appear between imaging sessions. These results indicate that thioflavine S-positive plaques appear and then are stable, supporting a dynamic feedback model of plaque growth.
Figures
Similar articles
-
In vivo multiphoton imaging reveals gradual growth of newborn amyloid plaques over weeks.Acta Neuropathol. 2011 Mar;121(3):327-35. doi: 10.1007/s00401-010-0787-6. Epub 2010 Dec 7. Acta Neuropathol. 2011. PMID: 21136067 Free PMC article.
-
Preclinical characterization of amyloid imaging probes with multiphoton microscopy.J Alzheimers Dis. 2006;9(3 Suppl):401-7. doi: 10.3233/jad-2006-9s345. J Alzheimers Dis. 2006. PMID: 16914878 Review.
-
In vivo imaging of reactive oxygen species specifically associated with thioflavine S-positive amyloid plaques by multiphoton microscopy.J Neurosci. 2003 Mar 15;23(6):2212-7. doi: 10.1523/JNEUROSCI.23-06-02212.2003. J Neurosci. 2003. PMID: 12657680 Free PMC article.
-
In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories.J Neuropathol Exp Neurol. 2003 Feb;62(2):137-45. doi: 10.1093/jnen/62.2.137. J Neuropathol Exp Neurol. 2003. PMID: 12578223
-
Alzheimer's disease: what multiphoton microscopy teaches us.Neuroscientist. 2002 Oct;8(5):386-90. doi: 10.1177/107385802236963. Neuroscientist. 2002. PMID: 12374422 Review.
Cited by
-
VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation.Nat Commun. 2023 Sep 20;14(1):5837. doi: 10.1038/s41467-023-41580-4. Nat Commun. 2023. PMID: 37730744 Free PMC article.
-
Long-Term Repeatable In Vivo Monitoring of Amyloid-β Plaques and Vessels in Alzheimer's Disease Mouse Model with Combined TPEF/CARS Microscopy.Biomedicines. 2022 Nov 16;10(11):2949. doi: 10.3390/biomedicines10112949. Biomedicines. 2022. PMID: 36428517 Free PMC article.
-
A Model of Discovery: The Role of Imaging Established and Emerging Non-mammalian Models in Neuroscience.Front Mol Neurosci. 2022 Apr 14;15:867010. doi: 10.3389/fnmol.2022.867010. eCollection 2022. Front Mol Neurosci. 2022. PMID: 35493325 Free PMC article. Review.
-
Optical Imaging of Beta-Amyloid Plaques in Alzheimer's Disease.Biosensors (Basel). 2021 Jul 29;11(8):255. doi: 10.3390/bios11080255. Biosensors (Basel). 2021. PMID: 34436057 Free PMC article. Review.
-
Visualization of neurofibrillary tangle maturity in Alzheimer's disease: A clinicopathologic perspective for biomarker research.Alzheimers Dement. 2021 Sep;17(9):1554-1574. doi: 10.1002/alz.12321. Epub 2021 Apr 2. Alzheimers Dement. 2021. PMID: 33797838 Free PMC article. Review.
References
-
- Denk W, Strickler JH, Webb WW. Two-photon laser scanning fluorescence microscopy. Science. 1990;248:73–76. - PubMed
-
- Esler WP, Stimson ER, Ghilardi JR, Vinters HV, Lee JP, Mantyh PW, Maggio JE. In vitro growth of Alzheimer's disease beta-amyloid plaques displays first-order kinetics. Biochemistry. 1996;35:749–757. - PubMed
-
- Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuther K. Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer's disease. J Mol Biol. 1991;218:149–163. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical