In Vivo Multiphoton Imaging of a Transgenic Mouse Model of Alzheimer Disease Reveals Marked Thioflavine-S-Associated Alterations in Neurite Trajectories
Abstract
Postmortem analyses of senile plaques reveal numerous dystrophic processes in their vicinity. We used in vivo multiphoton microscopy of a transgenic model of Alzheimer disease (AD) to simultaneously image senile plaques and nearby neuronal processes. Plaques were labeled by immunofluorescent staining or thioflavine-S and neuronal processes were labeled with a fluorescent dextran conjugate. Imaging of 3-dimensional volumes in the vicinity of plaques revealed subtle changes in neurite geometry in or near diffuse plaques. By contrast, disruptions in neurite morphology, including dystrophic neurites immediately surrounding plaques as well as major alterations in neurite trajectories, were seen in association with thioflavine-S-positive plaques. Nearly half of all labeled processes that came within 50 microm of a thioflavine-S-positive plaque were altered, suggesting a fairly large "halo" of neuropil alterations that extend beyond the discrete border of a thioflavine-S plaque. These results support the hypothesis that compact thioflavine-S-positive plaques disrupt the neuropil in AD.
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Studies of APP transgenic mice demonstrate plaque-associated dystrophic neurites with disrupted trajectories, glial activation, and free radical generation near plaques, each of which is also observed in AD brain.
“Studies of these transgenic mice demonstrate plaque-associated dystrophic neurites with disrupted trajectories, glial activation, and free radical generation near plaques, each of which is also observed in AD brain (Le et al., 2001;D'Amore et al., 2003;McLellan et al., 2003).”
From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as D'Amore et al., 2003
The 'halo' effect is observed in terms of both neurite trajectories and spine density.
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From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as D'Amore et al., 2003
We have not observed dendritic breakage in either our current studies or previous multiphoton investigations of plaque/neurite interactions using fluorescent dextrans or YFP as the marker for the neurites.
“In contrast, we have not observed dendritic breakage in either our current studies or previous multiphoton investigations of plaque/neurite interactions using fluorescent dextrans or YFP as the marker for the neurites (Brendza et al., 2003a,b;D'Amore et al., 2003).”
From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as D'Amore et al., 2003
Cites
Neuron loss in APP transgenic mice
Calhoun, M. E., Wiederhold, K.-H., Abramowski, D., Phinney, A. L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B., & Jucker, M. (1998) · Nature · doi:10.1038/27351 · Cited by 502 · see citing works
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Spires, T. L., Meyer-Luehmann, M., Stern, E. A., McLean, P. J., Skoch, J., Nguyen, P. T., Bacskai, B. J., & Hyman, B. T. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1879-05.2005 · Cited by 550 · see citing works
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Mandrekar, S., Jiang, Q., Lee, C. Y. D., Koenigsknecht-Talboo, J., Holtzman, D. M., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5572-08.2009 · Cited by 415 · see citing works
Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology
Perez-Nievas, B. G., Stein, T. D., Tai, H.-C., Dols-Icardo, O., Scotton, T. C., Barroeta-Espar, I., Fernandez-Carballo, L., de Munain, E. L., Perez, J., Marquie, M., et al. (2013) · Brain · doi:10.1093/brain/awt171 · Cited by 387 · see citing works
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Kim, J., Onstead, L., Randle, S., Price, R., Smithson, L., Zwizinski, C., Dickson, D. W., Golde, T., & McGowan, E. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4849-06.2007 · Cited by 359 · see citing works
“Although there is much debate regarding the role of amyloid in AD pathogenesis (Le et al., 2001; Caughey and Lansbury, 2003; D’Amore et al., 2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synapt…”
BackgroundSerrano-Pozo, A., Muzikansky, A., Gómez-Isla, T., Growdon, J. H., Betensky, R. A., Frosch, M. P., & Hyman, B. T. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182933788 · Cited by 226 · see citing works
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Stern, E. A., Bacskai, B. J., Hickey, G. A., Attenello, F. J., Lombardo, J. A., & Hyman, B. T. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0462-04.2004 · Cited by 210 · see citing works
Self-citationMeilandt, W. J., Ngu, H., Gogineni, A., Lalehzadeh, G., Lee, S.-H., Srinivasan, K., Imperio, J., Wu, T., Weber, M., Kruse, A. J., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1871-19.2019 · Cited by 210 · see citing works
“First, we looked at neuritic dystrophy around plaque (D’Amore et al., 2003) by fluorescent costaining using methoxyX04 to label plaque, anti-Iba1 to label microglia, and anti-Lamp1 to label dystrophic axons (Gowrishankar et al.”
BackgroundImpaired Spine Stability Underlies Plaque-Related Spine Loss in an Alzheimer's Disease Mouse Model
Spires-Jones, T. L., Meyer-Luehmann, M., Osetek, J. D., Jones, P. B., Stern, E. A., Bacskai, B. J., & Hyman, B. T. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070055 · Cited by 189 · see citing works
Self-citationDaRocha-Souto, B., Coma, M., Pérez-Nievas, B. G., Scotton, T. C., Siao, M., Sánchez-Ferrer, P., Hashimoto, T., Fan, Z., Hudry, E., Barroeta, I., et al. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.09.002 · Cited by 180 · see citing works
Self-citationSerrano-Pozo, A., William, C. M., Ferrer, I., Uro-Coste, E., Delisle, M.-B., Maurage, C.-A., Hock, C., Nitsch, R. M., Masliah, E., Growdon, J. H., et al. (2010) · Brain · doi:10.1093/brain/awq056 · Cited by 159 · see citing works
Self-citationAmyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations
Lombardo, J. A., Stern, E. A., McLellan, M. E., Kajdasz, S. T., Hickey, G. A., Bacskai, B. J., & Hyman, B. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10879.2003 · Cited by 149 · see citing works
Self-citationKoenigsknecht-Talboo, J., Meyer-Luehmann, M., Parsadanian, M., Garcia-Alloza, M., Finn, M. B., Hyman, B. T., Bacskai, B. J., & Holtzman, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4147-08.2008 · Cited by 149 · see citing works
García-Morales, V., González-Acedo, A., Melguizo-Rodríguez, L., Pardo-Moreno, T., Costela-Ruiz, V. J., Montiel-Troya, M., & Ramos-Rodríguez, J. J. (2021) · Biomedicines · doi:10.3390/biomedicines9121910 · Cited by 104 · see citing works
Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model
Garcia-Alloza, M., Dodwell, S. A., Meyer-Luehmann, M., Hyman, B. T., & Bacskai, B. J. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240468.12543.af · Cited by 99 · see citing works
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Gómez-Isla, T., & Frosch, M. P. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00642-9 · Cited by 96 · see citing works
Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice
Perez, S. E., He, B., Muhammad, N., Oh, K.-J., Fahnestock, M., Ikonomovic, M. D., & Mufson, E. J. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.10.002 · Cited by 80 · see citing works
Spires-Jones, T. L., Calignon, A. D., Meyer-Luehmann, M., Bacskai, B. J., & Hyman, B. T. (2011) · Methods · doi:10.1016/j.ymeth.2010.12.009 · Cited by 24 · see citing works
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- Authors
- D'Amore, J. D., Kajdasz, S. T., McLellan, M. E., Bacskai, B. J., Stern, E. A., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Corresponding author
- D'Amore, J. D.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02
- Volume
- 62
- Issue
- 2
- Pages
- 137-145
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2149077845
- Cited by
- 89
- References
- 1
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 8 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-08487, AG 15453, P01AG015453)
- 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 plaques, thioflavine S, transgenic mouse model, multiphoton microscopy, neurite morphology
- MeSH terms
- Aging, Alzheimer Disease, Animals, Axons, Cerebral Cortex, Dendrites, Dextrans, Disease Models, Animal, Fluorescent Dyes, Mice, Inbred C57BL, Mice, Transgenic, Thiazoles, Amyloid beta-Peptides, Neurites, Neuropil, Microscopy, Fluorescence, Multiphoton, Mice, Benzothiazoles, Plaque, Amyloid
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