Serum Levels of Glial Fibrillary Acidic Protein Association with Cognitive Impairment and Type 2 Diabetes

Ayala-Guerrero, Lorelei; García-delaTorre, Paola; Sánchez-García, Sergio; Guzmán-Ramos, Kioko

doi:10.1016/j.arcmed.2022.06.001

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…This observation is consistent with other studies in adults with diabetes. In a recent study of older adults, Ayala-Guerrero et al (2022) found significantly higher serum GFAP levels in people with T2D and cognitive impairment, compared to people without diabetes and who were cognitively unimpaired [48]. Interestingly, in this same study, serum GFAP levels followed a dose-response relationship where GFAP increased from cognitively unimpaired without T2D, to T2D only, to cognitively impaired only, and finally to T2D with cognitive impairment, suggesting that the presence of T2D confers added neuroimmune stress above and beyond that which underlies general cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study

Shapiro,

Coughlan,

Bettcher

et al. 2024

Endocrines

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Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study

Shapiro,

Coughlan,

Bettcher

et al. 2024

Endocrines

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“…Both EPA and DHA inhibited C3 expression in the ageing brain, while DHA, interestingly, was more effective than EPA in reducing GFAP but upregulating A2 marker S100A10 transcription. GFAP, a common marker of astroglia, was generally elevated in rodents and humans during ageing [37], which indicates a potential marker of cognitive impairment induced by ageing [38], AD [39], heart failure [40] and type 2 diabetes [41]. Previous studies showed that DHA regulated glial cell polarization by activating PPARγ in AD [42] and enhanced the expression of GFAP by the up-regulation of both PI3K/AKT-dependent FABP7-PPARγ interaction and MKP3 in astrocytes in young rat brains [43].…”

Section: Discussionmentioning

confidence: 99%

Omega-3 Polyunsaturated Fatty Acid Eicosapentaenoic Acid or Docosahexaenoic Acid Improved Ageing-Associated Cognitive Decline by Regulating Glial Polarization

et al. 2023

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Neuroinflammation induced by microglial and astrocyte polarizations may contribute to neurodegeneration and cognitive impairment. Omega (n)-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory and neuroprotective effects, but conflicting results were reported after different n-3 PUFA treatments. This study examined both the change in glial polarizations in ageing rats and the differential effects of two omega-3 PUFAs. The results showed that both PUFAs improved spatial memory in ageing rats, with docosahexaenoic acid (DHA) being more effective than eicosapentaenoic acid (EPA). The imbalance between microglial M1/M2 polarizations, such as up-regulating IBA1 and down-regulating CD206 and arginase-1 (ARG-1) was reversed in the hippocampus by both n-3 PUFAs, while the DHA effect on CD206 was stronger. Astrocyte A1 polarization presented increasing S100B and C3 but decreasing A2 parameter S100a10 in the ageing brain, which were restored by both PUFAs, while DHA was more effective on S100a10 than EPA. Consistent with microglial M1 activation, the concentration of proinflammatory cytokines tumor necrosis factor-(TNF) α, interleukin (IL)-1β and IL-6 were significantly increased, which were attenuated by DHA, while EPA only suppressed IL-6. In correlation with astrocyte changes, brain-derived neurotrophic factor precursor was increased in ageing rats, which was more powerfully down-regulated by DHA than EPA. In summary, enhanced microglial M1 and astrocytic A1 polarizations may contribute to increased brain proinflammatory cytokines, while DHA was more powerful than EPA to alleviate ageing-associated neuroimmunological changes, thereby better-improving memory impairment.

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“…During sustained inflammation, microglia phagocytose astrocytic endfeet and impair BBB function 125 . Impaired BBB is accompanied by elevated GFAP and serves as a biomarker of cognitive impairment in diabetes 126 . The co‐culture system of astrocyte and cerebral microvascular (CMEC) suggests that high glucose concentrations alter the expression of astrocyte Cx43 and increase VEGF secretion, resulting in impaired CMEC barrier properties 127 …”

Section: Gut Microbiota‐astrocyte Axis Connects T2dm With Cognitive D...mentioning

confidence: 99%

“…125 Impaired BBB is accompanied by elevated GFAP and serves as a biomarker of cognitive impairment in diabetes. 126 The co-culture system of astrocyte and cerebral microvascular (CMEC) suggests that high glucose concentrations alter the expression of astrocyte Cx43 and increase VEGF secretion, resulting in impaired CMEC barrier properties. 127 Gut microbiota-associated metabolites promote peripheral immune cells to alter the structural integrity of the BBB.…”

Section: Gut Microbiota and Astrocyte Are Critical Hubs To The Intest...mentioning

confidence: 99%

The gut microbiota‐astrocyte axis: Implications for type 2 diabetic cognitive dysfunction

Jiang

Long

et al. 2023

CNS Neurosci Ther

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Background Diabetic cognitive dysfunction (DCD) is one of the most insidious complications of type 2 diabetes mellitus, which can seriously affect the ability to self‐monitoring of blood glucose and the quality of life in the elderly. Previous pathological studies of cognitive dysfunction have focused on neuronal dysfunction, characterized by extracellular beta‐amyloid deposition and intracellular tau hyperphosphorylation. In recent years, astrocytes have been recognized as a potential therapeutic target for cognitive dysfunction and important participants in the central control of metabolism. The disorder of gut microbiota and their metabolites have been linked to a series of metabolic diseases such as diabetes mellitus. The imbalance of intestinal flora has the effect of promoting the occurrence and deterioration of several diabetes‐related complications. Gut microbes and their metabolites can drive astrocyte activation. Aims We reviewed the pathological progress of DCD related to the “gut microbiota‐astrocyte” axis in terms of peripheral and central inflammation, intestinal and blood–brain barrier (BBB) dysfunction, systemic and brain energy metabolism disorders to deepen the pathological research progress of DCD and explore the potential therapeutic targets. Conclusion “Gut microbiota‐astrocyte” axis, unique bidirectional crosstalk in the brain‐gut axis, mediates the intermediate pathological process of neurocognitive dysfunction secondary to metabolic disorders in diabetes mellitus.

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Serum Levels of Glial Fibrillary Acidic Protein Association with Cognitive Impairment and Type 2 Diabetes

Cited by 7 publications

References 56 publications

Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study

Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study

Omega-3 Polyunsaturated Fatty Acid Eicosapentaenoic Acid or Docosahexaenoic Acid Improved Ageing-Associated Cognitive Decline by Regulating Glial Polarization

The gut microbiota‐astrocyte axis: Implications for type 2 diabetic cognitive dysfunction

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