Neurofibrillary tangles and plaques are not accompanied by white matter pathology in aged triple transgenic-Alzheimer disease mice
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aging populations. Although senile plaques and neurofibrillary tangles are well-established hallmarks of AD, changes in cerebral white matter correlate with cognitive decline and may increase the risk of the development of dementia. We used the triple transgenic (3xTg)-AD mouse model of AD, previously used to show that white matter changes precede plaque formation, to test the hypothesis that MRI detectable changes occur in the corpus callosum, external capsule and the fornix. T2-weighted and diffusion tensor magnetic resonance imaging and histological stains were employed to assess white matter in older (11-17months) 3xTg-AD mice and controls. We found no statistically significant changes in white matter between 3xTg-AD mice and controls, despite well-developed neurofibrillary tangles and beta amyloid immunoreactive plaques. Myelin staining was normal in affected mice. These data suggest that the 3xTg-AD mouse model does not develop MRI detectable white matter changes at the ages we examined.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous pharmacokinetic modeling experiments suggest that EpoD has a residence time in the brain >10 days after a single dose at 3 mg/kg.
“Previous pharmacokinetic modeling experiments suggest that EpoD has a residence time in the brain >10 days after a single dose at 3mg/kg 30.”
From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [30]
In a previous study, prophylactic dosing with EpoD was sufficient to ameliorate axonal dystrophy.
“In a previous study, prophylactic dosing with EpoD was sufficient to ameliorate axonal dystrophy30.”
From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [30]
EpoD at 1 mg/kg was sufficient to reduce measures of tauopathy, neurodegeneration and axonal dystrophy in PS19 tau mice in previous work.
“The dose for this experiment was chosen based upon previous work by Brunden et. al. and Zhang et. al. in which EpoD at 1mg/kg was sufficient to reduce measures of tauopathy, neurodegeneration and axonal dystrophy in PS19 tau mice 30, 31.”
From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [30]
EpoD can promote axonal health by reducing axonal dystrophy, increasing ON microtubule density and normalizing fast axonal transport.
“Data from previous studies have found evidence that EpoD can promote axonal health by reducing axonal dystrophy, increasing ON microtubule density and normalizing fast axonal transport 30, 31.”
From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [30]
A previous DTI study did not observe any changes in diffusion metrics or alterations in myelin staining or white matter volumes across mice aged from 11 to 17 months.
“However, a previous DTI study did not observe any changes in diffusion metrics or alterations in myelin staining or WM volumes across mice aged from 11 to 17 months (Kastyak-Ibrahim et al., 2013).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Kastyak-Ibrahim et al., 2013
One study involving mice aged between 11 and 17 months found no WM DTI changes compared with controls.
“One study involving mice aged between 11 and 17 months found no WM DTI changes compared with controls (Kastyak-Ibrahim et al., 2013).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Kastyak-Ibrahim et al., 2013
One study found that the 3xTg-AD does not develop MRI detectable changes in late-life (11-17 months).
“In one study, the 3xTg-AD does not develop MRI detectable changes in late-life (11–17 months; Kastyak-Ibrahim et al., 2013)”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Kastyak-Ibrahim et al., 2013
In the 3xTg-AD model, at later time points, no significant difference in FA compared with control mice was detectable.
“or no significant difference in 3xTg-AD mice compared with control mice was detectable (Kastyak-Ibrahim et al., 2013)”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Kastyak-Ibrahim et al., 2013
Cites
Bartzokis, G., Sultzer, D., Lu, P. H., Nuechterlein, K. H., Mintz, J., & Cummings, J. L. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.09.005 · Cited by 363 · see citing works
White matter pathology isolates the hippocampal formation in Alzheimer's disease
Salat, D. H., Tuch, D. S., van der Kouwe, A. J. W., Greve, D. N., Pappu, V., Lee, S. Y., Hevelone, N. D., Zaleta, A. K., Growdon, J. H., Corkin, S., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.03.013 · Cited by 279 · see citing works
O'Dwyer, L., Lamberton, F., Bokde, A. L. W., Ewers, M., Faluyi, Y. O., Tanner, C., Mazoyer, B., O'Neill, D., Bartley, M., Collins, D. R., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021745 · Cited by 119 · see citing works
Gama Sosa, M. A., Gasperi, R. D., Rocher, A. B., Wang, A. C.-J., Janssen, W. G. M., Flores, T., Perez, G. M., Schmeidler, J., Dickstein, D. L., Hof, P. R., et al. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.090482 · Cited by 92 · see citing works
Zhang, J., Jones, M. V., McMahon, M. T., Mori, S., & Calabresi, P. A. (2012) · Magnetic Resonance in Medicine · doi:10.1002/mrm.23032 · Cited by 88 · see citing works
Chakravarthy, B., Gaudet, C., Ménard, M., Brown, L., Atkinson, T., LaFerla, F. M., Ito, S., Armato, U., Dal Prà, I., & Whitfield, J. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.09.056 · Cited by 52 · see citing works
Multiple pathologies are common in Alzheimer patients in clinical trials
Wang, B. W., Lu, E., Mackenzie, I. R. A., Assaly, M., Jacova, C., Lee, P. E., Beattie, B. L., & Hsiung, G. Y. R. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100015316 · Cited by 41 · see citing works
Lopes, J. P., Blurton-Jones, M., Yamasaki, T. R., Agostinho, P., & LaFerla, F. M. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-0993 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Imaging of cerebrovascular pathology in animal models of Alzheimer's disease
Klohs, J., Rudin, M., Shimshek, D. R., & Beckmann, N. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00032 · Cited by 82 · see citing works
Walter, S., Jumpertz, T., Hüttenrauch, M., Ogorek, I., Gerber, H., Storck, S. E., Zampar, S., Dimitrov, M., Lehmann, S., Lepka, K., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-1929-5 · Cited by 65 · see citing works
Manno, F. A. M., Isla, A. G., Manno, S. H. C., Ahmed, I., Cheng, S. H., Barrios, F. A., & Lau, C. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00039 · Cited by 49 · see citing works
Neuroimaging of mouse models of Alzheimer’s disease
Jullienne, A., Trinh, M. V., & Obenaus, A. (2022) · Biomedicines · doi:10.3390/biomedicines10020305 · Cited by 32 · see citing works
Snow, W. M., Dale, R., O’Brien-Moran, Z., Buist, R., Peirson, D., Martin, M., & Albensi, B. C. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170136 · Cited by 29 · see citing works
Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model
Nishioka, C., Liang, H.-F., Barsamian, B., & Sun, S.-W. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.01.007 · Cited by 30 · see citing works
“Tauopathy models have shown reductions in FA/RAD white matter in a pair of studies (Wells et al., 2015; Sahara et al., 2014), while the triple transgenic model (with combined APP/tau expression) does not reveal changes relative to controls (Kastyak-Ibrahim et al., 2013).”
Falangola, M. F., Nie, X., Ward, R., Dhiman, S., Voltin, J., Nietert, P. J., & Jensen, J. H. (2021) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2021.06.022 · Cited by 25 · see citing works
Diffusion MRI detects early brain microstructure abnormalities in 2-month-old 3×Tg-AD mice
Falangola, M. F., Nie, X., Ward, R., McKinnon, E. T., Dhiman, S., Nietert, P. J., Helpern, J. A., & Jensen, J. H. (2020) · NMR in Biomedicine · doi:10.1002/nbm.4346 · Cited by 22 · see citing works
Whittaker, H. T., Zhu, S., Di Curzio, D. L., Buist, R., Li, X.-M., Noy, S., Wiseman, F. K., Thiessen, J. D., & Martin, M. (2018) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2018.03.010 · Cited by 12 · see citing works
Self-citationMüller, H.-P., Roselli, F., Rasche, V., & Kassubek, J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00734 · Cited by 12 · see citing works
Falangola, M. F., Nie, X., Voltin, J., Ward, R., Dhiman, S., Nietert, P. J., & Jensen, J. H. (2022) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2022.09.002 · Cited by 6 · see citing works
Li, Y., Tang, Z., Yao, M., Ran, Y., & Qiu, Z. (2026) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00006
- Authors
- Kastyak-Ibrahim, M. Z., Di Curzio, D. L., Buist, R., Herrera, S. L., Albensi, B. C., Del Bigio, M. R., & Martin, M.
- Affiliations
- University of Manitoba (CA)
- Venue
- Magnetic Resonance Imaging
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 31
- Issue
- 9
- Pages
- 1515-1521
- ISSN
- 0730-725X (ISSN-L)
- OpenAlex
- W2039965538
- Cited by
- 23
- References
- 8
- Citations by year
- 2023: 1 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 2 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Magnetic Resonance Imaging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Society of Canada,
- Natural Sciences and Engineering Research Council
- Manitoba Health Research Council
- Canada Foundation for Innovation
- Manitoba Research and Innovation Fund
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, triple transgenic mouse model, white matter pathology, neurofibrillary tangles, amyloid plaques, corpus callosum, external capsule, fornix, myelin, diffusion tensor imaging, T2-weighted MRI, aging
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Fibers, Myelinated, Time Factors, Amyloid beta-Peptides, Neurofibrillary Tangles, Diffusion Magnetic Resonance Imaging, Mice, Diffusion Tensor Imaging, 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 ›
Are you an author, or do you see a problem with this page? Request a review
