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43/100

✓ Peer-reviewed alzhub usefulness score 43 out of 100. Drug development

Topic: Gut, metabolism and diet

Alzheimer’s disease is the most common form of dementia, and epidemiological studies support that type 2 diabetes (T2D) is a major contributor. The relationship between both diseases and the fact that Alzheimer’s disease (AD) does not have a successful treatment support the study on antidiabetic drugs limiting or slowing down brain complications in AD. Among these, liraglutide (LRGT), a glucagon-like peptide-1 agonist, is currently being tested in patients with AD in the Evaluating Liraglutide in Alzheimer’s Disease (ELAD) clinical trial. However, the effects of LRGT on brain pathology when AD and T2D coexist have not been assessed. We have administered LRGT (500 μg/kg/day) to a mixed murine model of AD and T2D (APP/PS1xdb/db mice) for 20 weeks. We have evaluated metabolic parameters as well as the effects of LRGT on learning and memory. Postmortem analysis included assessment of brain amyloid-β and tau pathologies, microglia activation, spontaneous bleeding and neuronal loss, as well as insulin and insulin-like growth factor 1 receptors. LRGT treatment reduced glucose levels in diabetic mice (db/db and APP/PS1xdb/db) after 4 weeks of treatment. LRGT also helped to maintain insulin levels after 8 weeks of treatment. While we did not detect any effects on cortical insulin or insulin-like growth factor 1 receptor m-RNA levels, LRGT significantly reduced brain atrophy in the db/db and APP/PS1xdb/db mice. LRGT treatment also rescued neuron density in the APP/PS1xdb/db mice in the proximity ( p = 0.008) far from amyloid plaques ( p < 0.001). LRGT reduced amyloid plaque burden in the APP/PS1 animals ( p < 0.001), as well as Aβ aggregates levels ( p = 0.046), and tau hyperphosphorylation ( p = 0.009) in the APP/PS1xdb/db mice. Spontaneous bleeding was also ameliorated in the APP/PS1xdb/db animals ( p = 0.012), and microglia burden was reduced in the proximity of amyloid plaques in the APP/PS1 and APP/PS1xdb/db mice ( p < 0.001), while microglia was reduced in areas far from amyloid plaques in the db/db and APP/PS1xdb/db mice ( p < 0.001). This overall improvement helped to rescue cognitive impairment in AD-T2D mice in the new object discrimination test ( p < 0.001) and Morris water maze ( p < 0.001). Altogether, our data support the role of LRGT in reduction of associated brain complications when T2D and AD occur simultaneously, as regularly observed in the clinical arena.

Key findings

While we did not detect any effects on cortical insulin or insulin-like growth factor 1 receptor m-RNA levels, LRGT significantly reduced brain atrophy in the db/db and APP/PS1xdb/db mice.
This overall improvement helped to rescue cognitive impairment in AD-T2D mice in the new object discrimination test ( p < 0.001) and Morris water maze ( p < 0.001).

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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. 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 25 of the 58 points we could judge it on, which is 43 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Frontiers in Aging Neuroscience)
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	3 / 5	2021 — within 6 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	Laboratory or animal study (title names “murine”) — scores zero
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 34975451)
Free to read	2 / 2	Free to read
Points	25 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100.
Total	43 / 100	—

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Cite this study APA, Vancouver, BibTeX · download .bib or .ris

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APA 7th

Carranza-Naval, M. J., del Marco, À., Hierro‐Bujalance, C., Alves-Martínez, P., Infante‐Garcia, C., Vargas-Soria, M., et al. (2021). Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer’s Disease and Type 2 Diabetes. Frontiers in Aging Neuroscience. https://doi.org/10.3389/fnagi.2021.741923

Vancouver

Carranza-Naval MJ, del Marco À, Hierro‐Bujalance C, Alves-Martínez P, Infante‐Garcia C, Vargas-Soria M, et al. Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer’s Disease and Type 2 Diabetes. Frontiers in Aging Neuroscience. 2021. doi:10.3389/fnagi.2021.741923. PMID: 34975451.

BibTeX

@article{carranzanaval2021-34975451,
  author  = {Carranza-Naval, María José and del Marco, Àngel and Hierro‐Bujalance, Carmen and Alves-Martínez, Pilar and Infante‐Garcia, Carmen and Vargas-Soria, María and Herrera, Marta and Barba-Cordoba, Belen and others},
  title   = {{Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer’s Disease and Type 2 Diabetes}},
  journal = {Frontiers in Aging Neuroscience},
  year    = {2021},
  doi     = {10.3389/fnagi.2021.741923},
  pmid    = {34975451},
  url     = {https://doi.org/10.3389/fnagi.2021.741923}
}

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