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GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease
Li Y, Duffy KB, Ottinger MA, Ray B, Bailey JA, Holloway HW, Tweedie D, Perry T et al.. Journal of Alzheimer's disease : JAD, 2010-01-01
Topic: Gut, metabolism and diet
Type 2 (T2) diabetes mellitus (DM) has been associated with an increased incidence of neurodegenerative disorders, including Alzheimer's disease (AD). Several pathological features are shared between diabetes and AD, including dysfunctional insulin signaling and a dysregulation of glucose metabolism. It has therefore been suggested that not only may the two conditions share specific molecular mechanisms but also that agents with proven efficacy in one may be useful against the other. Hence, the present study characterized the effects of a clinically approved long-acting analogue, exendin-4 (Ex-4), of the endogenous insulin releasing incretin, glucagon-like peptide-1 (GLP-1), on stress-induced toxicity in neuronal cultures and on amyloid-beta protein (Abeta) and tau levels in triple transgenic AD (3xTg-AD) mice with and without streptozocin (STZ)-induced diabetes. Ex-4 ameliorated the toxicity of Abeta and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. When 11 to 12.5 month old female 3xTg AD mice were challenged with STZ or saline, and thereafter treated with a continuous subcutaneous infusion of Ex-4 or vehicle, Ex-4 ameliorated the diabetic effects of STZ in 3xTg-AD mice, elevating plasma insulin and lowering both plasma glucose and hemoglobin A1c (HbA1c) levels. Furthermore, brain levels of Abeta protein precursor and Abeta, which were elevated in STZ 3xTg-AD mice, were significantly reduced in Ex-4 treated mice. Brain tau levels were unaffected following STZ challenge, but showed a trend toward elevation that was absent following Ex-4 treatment. Together, these results suggest a potential value of Ex-4 in AD, particularly when associated with T2DM or glucose intolerance.
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APA 7th
Li, Y., Duffy, K. B., Ottinger, M. A., Ray, B., Bailey, J. A., Holloway, H. W., et al. (2010). GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-2010-1314
Vancouver
Li Y, Duffy KB, Ottinger MA, Ray B, Bailey JA, Holloway HW, et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. Journal of Alzheimer's disease : JAD. 2010. doi:10.3233/jad-2010-1314. PMID: 20308787.
BibTeX
@article{li2010-20308787,
author = {Li, Y. and Duffy, K. B. and Ottinger, M. A. and Ray, B. and Bailey, J. A. and Holloway, H. W. and Tweedie, D. and Perry, T. and others},
title = {{GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2010},
doi = {10.3233/jad-2010-1314},
pmid = {20308787},
url = {https://doi.org/10.3233/jad-2010-1314}
}
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Key findings
- Type 2 (T2) diabetes mellitus (DM) has been associated with an increased incidence of neurodegenerative disorders, including Alzheimer's disease (AD).
- It has therefore been suggested that not only may the two conditions share specific molecular mechanisms but also that agents with proven efficacy in one may be useful against the other.
- Furthermore, brain levels of Abeta protein precursor and Abeta, which were elevated in STZ 3xTg-AD mice, were significantly reduced in Ex-4 treated mice.
- Together, these results suggest a potential value of Ex-4 in AD, particularly when associated with T2DM or glucose intolerance.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2010 — within 20 year(s) of the newest study here |
| 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20308787) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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