Induction of Tau Pathology by Intracerebral Infusion of Amyloid-β-Containing Brain Extract and by Amyloid-β Deposition in APP × Tau Transgenic Mice
Open accessAbstract
Alzheimer's disease presents morphologically with senile plaques, primarily made of extracellular amyloid-beta (A beta) deposits, and neurofibrillary lesions, which consist of intracellular aggregates of hyperphosphorylated tau protein. To study the in vivo induction of tau pathology, dilute brain extracts from aged A beta-depositing APP23 transgenic mice were intracerebrally infused in young B6/P301L tau transgenic mice. Six months after the infusion, tau pathology was induced in the injected hippocampus but also in brain regions well beyond the injection sites such as the entorhinal cortex and amygdala, areas with neuronal projection to the injection site. No or only modest tau induction was observed when brain extracts from aged nontransgenic control mice and aged tau-depositing B6/P301L transgenic mice were infused. To further study A beta-induced tau lesions B6/P301L tau transgenic mice were crossed with APP23 mice. Although A beta deposition in double-transgenic mice did not differ from single APP23 transgenic mice, double-transgenic mice revealed increased tau pathology compared to single B6/P301L tau transgenic mice predominately in areas with high A beta plaque load. The present results suggest that both extract-derived A beta species and deposited fibrillary A beta can induce the formation of tau neurofibrillary pathology. The observation that infused A beta can trigger the tau pathology in the absence of A beta deposits provides an explanation for the discrepancy between the neuroanatomical location of A beta deposits and the development and spreading of tau lesions in Alzheimer's disease brain.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Prior studies showed that either co-expressing APP and MAPT genes or using prion-like seeding paradigms led to exacerbated Aβ and tau pathologies.
“Previous studies have shown that either co-expressing APP and MAPT genes (3, 6, 23) or using prion-like seeding paradigms (4, 24, 25) led to exacerbated Aβ and tau pathologies.”
From Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation (2022) · cites this paper as [24]
The Abstract reports that crossing APP23 and tau-transgenic mice increased tau pathology, and that infusion of Aβ-containing extract induced tau pathology. It also states that Aβ deposition in the double-transgenic mice did not differ from single APP23 mice. Thus, this paper supports exacerbated tau pathology, but not exacerbated Aβ pathology. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAn induction of tau pathology was observed in P301L tau transgenic mice after infusion of an Aβ-containing brain extract from a 24-month-old APP23 mouse.
“A substantially increased number of NFTs was detected in P301L tau transgenic mice following injection of fibrillary Aβ42 peptides [30] and an induction of tau pathology was observed in the same line of tau transgenic mice after infusion of an Aβ-containing brain extract from a 24-month-old APP23 mouse [31].”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [31]
A limited number of studies have reported animal models that display both plaques and tangles.
“A limited number of studies have reported the development of animal models that display both plaques and tangles [10, 51, 91, 109, 121].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 30 · Cited by 281
Research works printed but not linked: 1
- Walker LC, Callahan MJ, Bian F, Durham RA, Roher AE, Lipinski WJ: Exogenous induction of cerebral beta-amyloidosis in betaAPP-trans- genic mice. Peptides 2002, 23:1241-1247
- Authors
- Bolmont, T., Clavaguera, F., Meyer-Luehmann, M., Herzig, M. C., Radde, R., Staufenbiel, M., Lewis, J., Hutton, M., Tolnay, M., & Jucker, M.
- Affiliations
- Hertie Institute for Clinical Brain Research (DE)
- University of Basel (CH)
- Novartis (Switzerland) (CH)
- Mayo Clinic (US)
- Corresponding author
- Jucker, Mathias
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 171
- Issue
- 6
- Pages
- 2012-2020
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2111123
- OpenAlex
- W2076482846
- Cited by
- 281
- References
- 30
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 18 · 2023: 12 · 2022: 9 · 2021: 16 · 2020: 27 · 2019: 14 · 2018: 18 · 2017: 21 · 2016: 14 · 2015: 14 · 2014: 14 · 2013: 15 · 2012: 11
- FWCI
- 8.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Bundesministerium für Bildung und Forschung (01GI0705)
- National Institutes of Health (5r01ns046355-03)
- National Institute of Neurological Disorders and Stroke (R01-NS046355, R01-NS46355)
- 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 › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau pathology, amyloid-beta, Alzheimer's disease, APP23 transgenic mice, intracerebral infusion, brain extracts, amyloid plaques, tau propagation, hippocampus, entorhinal cortex, amygdala
- MeSH terms
- Alzheimer Disease, Animals, Brain Chemistry, Cell Extracts, Female, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Tauopathies, Mice
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
