Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice
Cao D, Fukuchi K, Wan H, Kim H, Li L.. Neurobiology of aging, 2005-10-19
Topic: Brain proteins, microglia and lab models
Emerging evidence indicates that cholesterol metabolism affects the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) is obligatory in maintaining cholesterol homeostasis in the periphery. To investigate the role of LDLR in the development of AD-like behavior and pathology, Tg2576 mice, a well-characterized transgenic mouse model of AD, with different genotypes of LDLR were generated. Here we show that LDLR-deficient Tg2576 mice developed hypercholesterolemia and age-dependent cerebral beta-amyloidosis. Before the manifestation of amyloid-beta (Abeta) deposition, these mice displayed hyperactivity, reduced anxiety, and impaired spatial learning regardless of LDLR genotypes. After the manifestation of Abeta deposition, LDLR-deficient Tg2576 mice showed more spatial learning deficits than LDLR-intact Tg2576 mice. Although LDLR genotypes did not affect the expression level of the amyloid-beta precursor protein transgene, there was a significant increase in Abeta deposition accompanied with an increase of apoE expression in LDLR-deficient Tg2576 mice. Our results suggest that the LDLR plays a role in the development of Alzheimer-type learning impairment and amyloidosis and can be a novel therapeutic target for AD.
Key findings
- Emerging evidence indicates that cholesterol metabolism affects the pathogenesis of Alzheimer's disease (AD).
- Although LDLR genotypes did not affect the expression level of the amyloid-beta precursor protein transgene, there was a significant increase in Abeta deposition accompanied with an increase of apoE expression in LDLR-deficient Tg2576 mice.
- Our results suggest that the LDLR plays a role in the development of Alzheimer-type learning impairment and amyloidosis and can be a novel therapeutic target for AD.
Why it matters
In Tg2576 mice, lacking the LDL receptor led to high cholesterol, more amyloid deposits and worse spatial learning after amyloid appeared. This is animal work, so it does not yet show whether targeting the LDL receptor would help people.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 2006 — 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 | 5 / 7 | Cited 106 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.8 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 3 / 6 | Cited 3.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ling Li: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Alabama at Birmingham: institution h-index 1,118 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16236385) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Cao, D., Fukuchi, K., Wan, H., Kim, H., & Li, L. (2006). Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2005.09.011
Vancouver
Cao D, Fukuchi K, Wan H, Kim H, Li L. Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice. Neurobiology of aging. 2006. doi:10.1016/j.neurobiolaging.2005.09.011. PMID: 16236385.
BibTeX
@article{cao2006-16236385,
author = {Cao, D. and Fukuchi, K. and Wan, H. and Kim, H. and Li, L.},
title = {{Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice}},
journal = {Neurobiology of aging},
year = {2006},
doi = {10.1016/j.neurobiolaging.2005.09.011},
pmid = {16236385},
url = {https://doi.org/10.1016/j.neurobiolaging.2005.09.011}
}
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