Evidence map›Paper›PMID 40948809›Full record

ArticleFrontiers in neuroscience2025

Systemic lipid and glucose modulation differentially affects cognitive function and neuroinflammation in a mouse model of Alzheimer's disease.

Demos Kynigopoulos, Eleni Fella, Lucy Shahabian, Christiana C Christodoulou, Revekka Papacharalampous, Konstantinos Diskos, Lida Evmorfia Vagiaki, Kyriaki Sidiropoulou, Menelaos Pipis, Kleopas A Kleopa and 1 more

Abstract read
In one paragraph

Article in Frontiers in neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Demos KynigopoulosNeuropathology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Eleni FellaNeuropathology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Lucy ShahabianNeuropathology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Christiana C ChristodoulouNeuroepidemiology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Revekka PapacharalampousNeuropathology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Konstantinos DiskosDepartment of Biology, University of Crete, Heraklion, Greece.
Lida Evmorfia VagiakiDepartment of Biology, University of Crete, Heraklion, Greece.
Kyriaki SidiropoulouDepartment of Biology, University of Crete, Heraklion, Greece.
Menelaos PipisNeuropathology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Kleopas A KleopaDepartment of Neuroscience, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Elena PanayiotouNeuropathology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and cognitive decline. Increasing evidence implicates systemic metabolic dysregulation in AD pathogenesis, yet it remains unclear whether modulation of peripheral lipid and glucose metabolism can alter disease progression. Methods: We investigated the effects of two FDA-approved metabolic agents-Alirocumab, a PCSK9 inhibitor that lowers LDL cholesterol, and Gliclazide, a sulfonylurea that enhances insulin secretion-in male 5xFAD mice, a transgenic model of AD. Animals received chronic treatment for five months. Behavioral testing, hippocampal electrophysiology, ELISA, lipidomics, and adipokine profiling were performed to assess cognitive, synaptic, and molecular outcomes. Results: Alirocumab significantly improved spatial working memory, restored hippocampal long-term potentiation, and normalized synaptophysin expression. Gliclazide reduced neuroinflammation and partially preserved glial and neuronal markers. Both treatments decreased amyloid burden and modulated adipokine levels, with Alirocumab elevating leptin and omentin in brain and serum. Lipidomic profiling of visceral adipose tissue revealed distinct lipid remodeling and highlighted candidate pathways linking systemic metabolism to central nervous system outcomes. Discussion: These findings demonstrate that systemic modulation of lipid and glucose metabolism can influence neurodegenerative and synaptic processes in AD. The results support metabolic interventions as a potential strategy to modify AD progression through peripheral-central metabolic crosstalk.

Indexed as

5xFAD mouse modelAlirocumabAlzheimer’s diseaseGliclazideglucose metabolismlipid metabolismneuroinflammationsynaptic plasticity

Identifiers

PMID40948809
PMCPMC12426080

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.