The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease
Kuo YM, Beach TG, Sue LI, Scott S, Layne KJ, Kokjohn TA, Kalback WM, Luehrs DC et al.. Molecular medicine (Cambridge, Mass.), 2001-09-01
Topic: Amyloid, tau and blood-test diagnosis
Background High levels of A beta in the cerebral cortex distinguish demented Alzheimer's disease (AD) from nondemented elderly individuals, suggesting that decreased amyloid-beta (A beta) peptide clearance from the brain is a key precipitating factor in AD. Materials and methods The levels of A beta in brain and plasma as well as apolipoprotein E (ApoE) in brain were investigated by enzyme-linked immunosorbent assay (ELISA) and Western blotting at various times during the life span of the APP23 transgenic (Tg) and control mice. Histochemistry and immunocytochemistry were used to assess the morphologic characteristics of the brain parenchymal and cerebrovascular amyloid deposits and the intracellular amyloid precursor protein (APP) deposits in the APP23 Tg mice. Results No significant differences were found in the plasma levels of A beta between the APP23 Tg and control mice from 2-20 months of age. In contrast, soluble A beta levels in the brain were continually elevated, increasing 4-fold at 2 months and 33-fold in the APP23 Tg mice at 20 months of age when compared to the control mice. Soluble A beta42 was about 60% higher than A beta40. In the APP23 Tg mice, insoluble A beta40 remained at basal levels in the brain until 9 months and then rose to 680 microg/g cortex by 20 months. Insoluble A beta40 was negligible in non-Tg mice at all ages. Insoluble A beta42 in APP23 Tg mice rose to 60 microg/g cortex at 20 months, representing 24 times the control A beta42 levels. Elevated levels of ApoE in the brain were observed in the APP23 Tg mice at 2 months of age, becoming substantially higher by 20 months. ApoE colocalized with A beta in the plaques. Beta-amyloid precursor protein (betaAPP) deposits were detected within the neuronal cytoplasm from 4 months of age onward. Amyloid angiopathy in the APP23 Tg mice increased markedly with age, being by far more severe than in the Tg2576 mice. Conclusions We suggest that the APP23 Tg mouse may develop an earlier blockage in A beta clearance than the Tg2576 mice, resulting in a more severe accumulation of A beta in the perivascular drainage pathways and in the brain. Both Tg mice reflect decreased A beta elimination and as models for the amyloid cascade they are useful to study AD pathophysiology and therapy.
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APA 7th
Kuo, Y. M., Beach, T. G., Sue, L. I., Scott, S., Layne, K. J., Kokjohn, T. A., et al. (2001). The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease. Molecular medicine (Cambridge, Mass.). https://doi.org/10.1007/bf03401867
Vancouver
Kuo YM, Beach TG, Sue LI, Scott S, Layne KJ, Kokjohn TA, et al. The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease. Molecular medicine (Cambridge, Mass.). 2001. doi:10.1007/bf03401867. PMID: 11778650.
BibTeX
@article{kuo2001-11778650,
author = {Kuo, Y. M. and Beach, T. G. and Sue, L. I. and Scott, S. and Layne, K. J. and Kokjohn, T. A. and Kalback, W. M. and Luehrs, D. C. and others},
title = {{The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease}},
journal = {Molecular medicine (Cambridge, Mass.)},
year = {2001},
doi = {10.1007/bf03401867},
pmid = {11778650},
url = {https://doi.org/10.1007/bf03401867}
}
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Key findings
- Background High levels of A beta in the cerebral cortex distinguish demented Alzheimer's disease (AD) from nondemented elderly individuals, suggesting that decreased amyloid-beta (A beta) peptide clearance from the brain is a key precipitating factor in AD.
- Results No significant differences were found in the plasma levels of A beta between the APP23 Tg and control mice from 2-20 months of age.
- In contrast, soluble A beta levels in the brain were continually elevated, increasing 4-fold at 2 months and 33-fold in the APP23 Tg mice at 20 months of age when compared to the control mice.
- Conclusions We suggest that the APP23 Tg mouse may develop an earlier blockage in A beta clearance than the Tg2576 mice, resulting in a more severe accumulation of A beta in the perivascular drainage pathways and in the brain.
Why it matters
In APP23 mice engineered to make human amyloid, soluble amyloid-beta in the brain was 4 times control levels at 2 months and 33 times at 20 months, while blood levels never differed from normal mice; insoluble deposits climbed sharply after 9 months, ApoE rose and sat inside plaques, and amyloid in blood vessel walls became far more severe than in another model, Tg2576. The authors suggest this points to an early blockage in clearing amyloid from the brain, though the study measured amyloid levels rather than clearance itself. All findings are in mice and no treatment was tested.
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Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular medicine (Cambridge, Mass.)) |
| Journal's citation record | 2 / 4 | Molecular Medicine: journal h-index 158 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2001 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 90 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.3 citations a year over 27 year(s) since 2001 |
| Impact for its field and year | 2 / 6 | Cited 2.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alex E. Roher: h-index 70 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Southampton: institution h-index 938 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 11778650) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
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