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Cited by 75Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsBarrier Structure and Function Studies

Peripheral Inflammation and Insulin Resistance: Their Impact on Blood–Brain Barrier Integrity and Glia Activation in Alzheimer’s Disease

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Ponce-Lopez, Teresa·2025·International Journal of Molecular Sciences
DOI 10.3390/ijms26094209PMC PMC12072112
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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and synaptic dysfunction. The accumulation of amyloid beta (Aβ) plaques and hyperphosphorylated tau protein leads to neuronal dysfunction, neuroinflammation, and glial cell activation. Emerging evidence suggests that peripheral insulin resistance and chronic inflammation, often associated with type 2 diabetes (T2D) and obesity, promote increased proinflammatory cytokines, oxidative stress, and immune cell infiltration. These conditions further damage the blood–brain barrier (BBB) integrity and promote neurotoxicity and chronic glial cell activation. This induces neuroinflammation and impaired neuronal insulin signaling, reducing glucose metabolism and exacerbating Aβ accumulation and tau hyperphosphorylation. Indeed, epidemiological studies have linked T2D and obesity with an increased risk of developing AD, reinforcing the connection between metabolic disorders and neurodegeneration. This review explores the relationships between peripheral insulin resistance, inflammation, and BBB dysfunction, highlighting their role in glial activation and the exacerbation of AD pathology.

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Authors
Ponce-Lopez, T.
Affiliations
Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan 52786, Mexico
ORCID
Ponce-Lopez, Teresa
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2025-04-29
Volume
26
Issue
9
Pages
4209
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms26094209
PMC
PMC12072112
OpenAlex
W4409944578
Cited by
75
References
46
Citations by year
2026: 58 · 2025: 17
FWCI
6.73
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
The Investigaciones y Estudios Superiores S C
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
Alzheimer's disease, insulin resistance, blood-brain barrier integrity, glial activation, neuroinflammation, type 2 diabetes, obesity, peripheral inflammation, amyloid-beta, tau hyperphosphorylation, inflammatory cytokines, oxidative stress, immune cell infiltration, glucose metabolism
MeSH terms
Alzheimer Disease, Animals, Blood-Brain Barrier, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin Resistance, Neuroglia

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