AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin
Open accessAbstract
Increasing data suggest a crucial relationship between glycolipid metabolic disorder and neuropsychiatric injury. The aim of this study is to investigate the behavioral performance changes and neuropathological injuries in mice challenged with high-fat diet (HFD) and streptozotocin (STZ). The glucose metabolism indicators and behavioral performance were detected. The mRNA expression of IL-1β, IL-6, TNF-α, ocln, zo-1, and clnds and protein expression of APP, p-Tau, p-IRS1, p-AKT, p-ERK, and TREM1/2 were measured. The fluorescence intensities of MAP-2, NeuN, APP, p-Tau, GFAP, and IBA-1 were observed. The results showed that combination of HFD and STZ/I.P. could induce glucose metabolic turmoil and Alzheimer's disease (AD)-like neuropsychiatric dysfunction in mice, as indicated by the increased concentrations of fasting blood glucose and impaired learning and memory ability. Moreover, the model mice presented increased levels of APP, p-Tau, p-IRS1, TREM2, IL-1β, IL-6, TNF-α, ocln, zo-1, and clnds; decreased levels of p-AKT, p-ERK, and TREM1; and neuron damage and the hyperactivation of astrocytes and microglia in the hippocampus as compared with control mice. Only male mice were used in this study. Although AD and type 2 diabetes mellitus (T2DM) are distinct pathologies, our results suggested that combination of HFD and STZ/I.P., a widely used T2DM modeling method, could successfully induce AD-like behavioral impairments and neuropathological injuries in mice; the mechanism might be involved with neuroinflammation and its associated dysfunction of IRS1/AKT/ERK signaling pathway. Our findings further support the potential overlap between T2DM and AD pathophysiology, providing insight into the mechanisms underlying the comorbidity of these diseases.
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Written from the paper’s full text.
TL;DR
Combining high-fat diet with intraperitoneal streptozotocin in male C57BL/6 mice produced hyperglycemia, hyperinsulinemia, insulin resistance, and AD-like behavioral and neuropathological changes. The authors propose neuroinflammation and IRS1/AKT/ERK signaling dysfunction as possible mechanisms linking T2DM and AD.
Key findings
- Model mice had significantly increased fasting blood glucose, serum insulin, and HOMA-IR versus controls (Fig. 1B–D; n = 8 per group; p < 0.05/0.01).
- Model mice showed impaired cognition: decreased novel object recognition index, decreased novel arm preference in the Y-maze, and in the Morris water maze decreased target-quadrant distance and increased latency to the target quadrant; no significant open-field test differences were found (Fig. 2; n = 8 per group).
- Model mice had reduced hippocampal Map-2 and NeuN immunofluorescence, reduced mRNA for ocln, zo-1, and clnds in hippocampus and PFC, increased APP and p-Tau by immunofluorescence/Western blot, and increased IBA-1+ microglia, activated microglia ratio, CD68+ microglia, and GFAP+ astrocytes (Fig. 3–5; n = 3 per group).
- Model mice had increased p-IRS1/IRS1, decreased p-AKT/AKT and p-ERK/ERK, decreased TREM1, increased TREM2, and increased IL-1β, IL-6, and TNF-α mRNA in hippocampus and PFC (Fig. 6–7; n = 3 per group).
Methods
- Sixteen male C57BL/6 mice, aged 6 weeks, were randomized to control standard chow (3.766 kcal/g) or model high-fat diet (60% of calories from fat, 5 kcal/g) for 8 weeks; model mice then received intraperitoneal STZ (100 mg/kg), while controls received buffer.
- Behavioral tests were open-field, novel object recognition, Y-maze, and Morris water maze; serum glucose and insulin were measured and HOMA-IR calculated; immunofluorescence, Western blotting, and qPCR were used for neuronal, AD-like, glial, insulin-signaling, TREM1/2, inflammatory, and BBB-related markers.
- Two-group comparisons used Student’s t test plus Wilcoxon rank-sum test; comparisons of more than two groups used two-way/repeated-measures ANOVA with Bonferroni post hoc; data are mean ± SEM, with p < 0.05 considered significant.
Limitations
- Stated by the paper: the mouse model may not fully represent human AD; mechanisms and interactions need further study; genetic and environmental factors were not explored; sample size was relatively small; only hippocampus and PFC were examined; mRNA data do not directly equate to protein function or localization, and BBB permeability was not directly evaluated; only male mice were used, so findings may not generalize to females.
- Evident in the text: the abstract states ocln, zo-1, and clnds levels were increased, whereas the Results report their mRNA expression was reduced in model mice, an internal inconsistency.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Claims the paper makes
20 of 43 cited sources checked · 3 supported · 1 flagged · accuracy not yet measured
- Premisecitation
Detecting the expression of Map-2 and NeuN helps determine the extent of neuronal damage and degeneration.
“Map-2 and NeuN are the neuronal marker proteins used to assess the morphology and function of neurons, and detecting the expression of Map-2 and NeuN could help know the extent of neuronal damage and degeneration in the present study (Götz and Ittner, 2008; Ghatak et al., 2019; Sattarov et al., 2023).”
Quote in the paperSubstantial claim2 of 3 sources checked- cites Götz and Ittner, 2008 source
- cites Ghatak et al., 2019 source
The Results section reports reduced neurite area in Alzheimer’s disease neurons measured with MAP2 antibody labeling, supporting the use of MAP2 to assess neuronal morphology. The paper’s immunocytochemistry methods list other neuronal markers but not NeuN, and our copy does not show that measuring expression of both MAP2 and NeuN determines the extent of neuronal damage or degeneration. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites Sattarov et al., 2023 source
The Results table lists MAP-2 and NeuN as markers of induced neurons. The Discussion (AD-related features in iN cells) reports that fewer MAP2-positive cells under APP overexpression may suggest decreased cell survival. It does not establish that measuring MAP-2 and NeuN together determines the extent of neuronal damage or degeneration; page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
Hyperglycemia and insulin resistance are important metabolic factors in the pathogenesis of AD.
“Hyperglycemia and insulin resistance, which are typical clinical features of T2DM, have also been increasingly recognized as an important metabolic index in the pathogenesis of AD (Grodstein et al., 2001; Luchsinger et al., 2004).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites Grodstein et al., 2001 source
The introduction (section D; page unavailable) reports a possible association of diabetes or hyperinsulinemia with poor cognition, and the Results report poorer cognitive performance among women with type 2 diabetes. These passages do not establish that hyperglycemia or insulin resistance are factors in the pathogenesis of Alzheimer’s disease; the paper examines cognitive test performance, not AD pathogenesis. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites Luchsinger et al., 2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingown data
In Mod mice, protein expression of TREM2 was significantly increased in the hippocampus and PFC compared with control mice.
“Compared to the Con mice, the Mod mice exhibited a significant decrease in the protein expression of TREM1 and an obvious increase in the protein expression of TREM2 in both the hippocampus (Fig. 7A,B) and PFC (Fig. 7D,E), indicating an imbalanced expression of TREM1/2 induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Findingown data
The number of IBA-1-positive cells was significantly increased in the hippocampus of model mice compared with control mice.
“the number of IBA-1–positive cells (Fig. 5B) and the ratio of activated microglia cells to the total number of microglia cells (Fig. 5C) were both significantly increased in the hippocampus of Mod mice.”
Quote in the paperSubstantial claim - Findingown data
The protein expression levels of APP, p-Tau, and Tau in the hippocampal and PFC tissues were significantly increased in model mice compared with control mice.
“the protein expression levels of APP, p-Tau, and Tau in the hippocampal and PFC tissues of mice in the Mod group were significantly increased compared with the Con ones”
Quote in the paperSubstantial claim
- Findingown data
Mod mice showed decreased learning and memory ability in the NOR, Y-maze, and MWM tasks compared with control mice.
“Moreover, the model mice showed decreased learning and memory ability in the NOR, Y-maze, and MWM tasks, although there was no significant difference between groups in the behavioral performance in the OFT.”
Quote in the paperSubstantial claim - Findingown data
In the Morris water maze probe trial, model mice showed a decreased distance traveled in the target quadrant compared with control mice.
“the Mod mice showed a decreased distance traveled in the target quadrant and an increased latency found in the target quadrant in the probe trial (Fig. 2I–K).”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, mRNA expression of IL-6 was remarkably increased in the hippocampus and PFC compared with control mice.
“Additionally, as depicted in Figure 7C,F, the mRNA expression levels of the inflammatory factors IL-1β, IL-6, and TNF-α in the hippocampus and PFC of Mod mice were all remarkably increased as compared with the Con ones, suggesting an increased inflammatory response induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Findingown data
In mice fed a high-fat diet followed by intraperitoneal streptozotocin, fasting blood glucose levels were significantly increased compared with control mice.
“the mice in the Mod group exhibited a significant increased blood glucose levels and serum levels of insulin when compared with the Con group, as shown in Figure 1B,C.”
Quote in the paperSubstantial claim - Findingown data
The ratio of activated microglia cells to the total number of microglia cells was significantly increased in the hippocampus of model mice compared with control mice.
“the number of IBA-1–positive cells (Fig. 5B) and the ratio of activated microglia cells to the total number of microglia cells (Fig. 5C) were both significantly increased in the hippocampus of Mod mice.”
Quote in the paperSubstantial claim - Findingown data
p-Tau immunofluorescent staining was increased in the hippocampus of model mice compared with control mice.
“the immunofluorescent staining of p-Tau was also increased in the hippocampus of Mod mice as compared with the Con mice (Fig. 4C,D).”
Quote in the paperSubstantial claim - Findingown data
The relative protein expression of p-ERK/ERK was decreased in the hippocampus and PFC of model mice compared with control mice.
“the relative protein expression of p-AKT/AKT and p-ERK/ERK were both decreased in the hippocampus and PFC of Mod mice when compared with the Con mice (Fig. 6A–C)”
Quote in the paperSubstantial claim - Findingown data
In mice given the combination of HFD and STZ/I.P. (Mod mice), protein expression of TREM1 was significantly decreased in the hippocampus and PFC compared with control mice.
“Compared to the Con mice, the Mod mice exhibited a significant decrease in the protein expression of TREM1 and an obvious increase in the protein expression of TREM2 in both the hippocampus (Fig. 7A,B) and PFC (Fig. 7D,E), indicating an imbalanced expression of TREM1/2 induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Findingown data
The model group exhibited significantly lower Map-2 fluorescence intensity in the hippocampal region than the control group.
“the Mod group exhibited significantly lower fluorescence intensity for Map-2 in the hippocampal region, suggesting a reduction in the expression of this neuronal marker compared with the control group.”
Quote in the paperSubstantial claim - Findingown data
The relative protein expression of p-IRS1/IRS1 was increased in the hippocampus and PFC of model mice compared with control mice.
“the relative protein expression of p-IRS1/IRS1 was increased in the hippocampus and PFC of Mod mice”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, expression levels of Aβ were significantly increased in the hippocampus and PFC compared with control mice.
“the results of Western blot and immunofluorescence staining both indicated that the expression levels of Aβ and p-Tau were significantly increased in the hippocampus and PFC of Mod mice as compared with the Con mice.”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, protein expression of p-AKT/AKT was decreased in the hippocampus and PFC compared with control mice.
“the results of the present study showed that the protein expression levels of p-IRS1/IRS1 were increased, while the levels of p-AKT/AKT and p-ERK/ERK were decreased in the hippocampus and PFC of mice induced by the combination of HFD and STZ/I.P.”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, immunofluorescence staining of Map-2 and NeuN in hippocampal tissue was significantly reduced compared with control mice.
“immunofluorescence staining of Map-2 and NeuN in the hippocampal tissue of Mod mice exhibited a significant reduction, indicating that the combined effect of HFD and STZ/I.P. can induce hippocampal neuronal damage in mice”
Quote in the paperSubstantial claim - Findingown data
In the Morris water maze probe trial, model mice showed an increased latency to the target quadrant compared with control mice.
“the Mod mice showed a decreased distance traveled in the target quadrant and an increased latency found in the target quadrant in the probe trial (Fig. 2I–K).”
Quote in the paperSubstantial claim - Findingown data
NeuN immunofluorescent staining was reduced in the hippocampus of model mice compared with control mice.
“the immunofluorescent staining of NeuN was also reduced in the hippocampus of Mod mice as compared with the Con mice (Fig. 3C,D)”
Quote in the paperSubstantial claim - Findingown data
APP immunofluorescence intensity was significantly increased in the hippocampus of model mice compared with control mice.
“there has been a significant increase in APP immunofluorescence intensity in the hippocampus of Mod mice.”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, the number of activated microglia cells in the hippocampus was significantly increased compared with control mice.
“the results of our present study showed that the number of activated microglia cells and the number of astrocyte cells were both significantly increased in the hippocampus of Mod mice as compared with the Con mice, indicating that combination of HFD and STZ/I.P. could promote the activation of microglia and astrocytes in the hippocampus of mice.”
Quote in the paperSubstantial claim - Findingown data
Model mice exhibited a decreased novel arm preference index in the Y-maze compared with control mice.
“the Mod mice exhibited a significant decrease in the novel object recognition index (Fig. 2E,F), together with a decreased novel arm preference index (Fig. 2G,H).”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, expression levels of p-Tau were significantly increased in the hippocampus and PFC compared with control mice.
“the results of Western blot and immunofluorescence staining both indicated that the expression levels of Aβ and p-Tau were significantly increased in the hippocampus and PFC of Mod mice as compared with the Con mice.”
Quote in the paperSubstantial claim - Findingown data
GFAP-positive cell immunofluorescent staining was increased in the hippocampus of model mice compared with control mice.
“the immunofluorescent staining of GFAP-positive cells was also increased in the hippocampus of Mod mice as compared with the Con mice (Fig. 5E,F)”
Quote in the paperSubstantial claim - Findingown data
Model mice exhibited a significant decrease in the novel object recognition index compared with control mice.
“the Mod mice exhibited a significant decrease in the novel object recognition index (Fig. 2E,F), together with a decreased novel arm preference index (Fig. 2G,H).”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, mRNA expression of IL-1β was remarkably increased in the hippocampus and PFC compared with control mice.
“Additionally, as depicted in Figure 7C,F, the mRNA expression levels of the inflammatory factors IL-1β, IL-6, and TNF-α in the hippocampus and PFC of Mod mice were all remarkably increased as compared with the Con ones, suggesting an increased inflammatory response induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Findingown data
There was no significant difference between Mod and control groups in behavioral performance in the OFT.
“Moreover, the model mice showed decreased learning and memory ability in the NOR, Y-maze, and MWM tasks, although there was no significant difference between groups in the behavioral performance in the OFT.”
Quote in the paperNot a substantial claim - Findingown data
The model group demonstrated a higher prevalence of CD68+ microglia than the control group.
“the Mod group demonstrated a higher prevalence of CD68+ microglia than the Con group (Fig. 5D).”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, the number of astrocyte cells in the hippocampus was significantly increased compared with control mice.
“the results of our present study showed that the number of activated microglia cells and the number of astrocyte cells were both significantly increased in the hippocampus of Mod mice as compared with the Con mice, indicating that combination of HFD and STZ/I.P. could promote the activation of microglia and astrocytes in the hippocampus of mice.”
Quote in the paperSubstantial claim - Findingown data
In mice fed a high-fat diet followed by intraperitoneal streptozotocin, serum insulin levels were significantly increased compared with control mice.
“the mice in the Mod group exhibited a significant increased blood glucose levels and serum levels of insulin when compared with the Con group, as shown in Figure 1B,C.”
Quote in the paperSubstantial claim - Findingown data
There was no significant difference between model and control mice in total moving distance, average speed, or line crossing in the open-field test.
“there was no significant difference between the two groups in the total moving distance, average speed, and line crossing in the OFT.”
Quote in the paperNot a substantial claim - Findingown data
In Mod mice, the HOMA-IR index was significantly increased compared with control mice.
“Consistently, in the present study, our results showed that combination of HFD and STZ/I.P. could induce a significant increase in blood glucose level, serum insulin, and the HOMA-IR index in mice.”
Quote in the paperSubstantial claim - Findingown data
The mRNA expression levels of ocln, zo-1, and clnds in the hippocampus and PFC of model mice were all remarkably reduced compared with control mice.
“the mRNA expression levels of ocln, zo-1, and clnds in the hippocampus and PFC of Mod mice were all remarkably reduced compared with the Con ones”
Quote in the paperSubstantial claim - Findingown data
In Mod mice, mRNA expression of TNF-α was remarkably increased in the hippocampus and PFC compared with control mice.
“Additionally, as depicted in Figure 7C,F, the mRNA expression levels of the inflammatory factors IL-1β, IL-6, and TNF-α in the hippocampus and PFC of Mod mice were all remarkably increased as compared with the Con ones, suggesting an increased inflammatory response induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Findingown data
The relative protein expression of p-AKT/AKT was decreased in the hippocampus and PFC of model mice compared with control mice.
“the relative protein expression of p-AKT/AKT and p-ERK/ERK were both decreased in the hippocampus and PFC of Mod mice when compared with the Con mice (Fig. 6A–C)”
Quote in the paperSubstantial claim - Findingown data
The HOMA-IR index was significantly increased in model mice compared with control mice.
“the results showed that the HOMA-IR index was significantly increased in the Mod mice as compared with the Con mice, as shown in Figure 1D.”
Quote in the paperSubstantial claim - Interpretationown data
The combination of HFD and STZ/I.P. induces hippocampal neuronal damage in mice.
“immunofluorescence staining of Map-2 and NeuN in the hippocampal tissue of Mod mice exhibited a significant reduction, indicating that the combined effect of HFD and STZ/I.P. can induce hippocampal neuronal damage in mice”
Quote in the paperSubstantial claim - Interpretationown data
The combination of HFD and STZ/I.P. induces an imbalanced expression of TREM1/2 in the hippocampus and PFC of mice.
“indicating an imbalanced expression of TREM1/2 induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Interpretationown data
The findings support a potential overlap between T2DM and AD pathophysiology.
“Our findings further support the potential overlap between T2DM and AD pathophysiology, providing insight into the mechanisms underlying the comorbidity of these diseases.”
Quote in the paperSubstantial claim- Rests on an assumption: The combination of high-fat diet and intraperitoneal streptozotocin is a widely used and valid method for modeling type 2 diabetes mellitus in mice.
- Rests on an assumption: Findings in this mouse model can inform the pathophysiology of the comorbidity of type 2 diabetes mellitus and Alzheimer's disease in humans.
- Interpretationown data
The combination of high-fat diet and intraperitoneal streptozotocin could induce neuron damage in the hippocampus of mice.
“indicating that combination of HFD and STZ/I.P. could induce neuron damage in the hippocampus of mice.”
Quote in the paperSubstantial claim - Premisecitation
STZ induces behavioral impairments in rodents.
“the results of our previous studies suggested that STZ could induce behavioral impairments in rodents (Qi et al., 2021; Fan et al., 2022; X. Gao et al., 2023b).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
The combination of HFD and STZ/I.P. induces AD-related pathology in mice.
“These results indicated that combination of HFD and STZ/I.P. could induce an AD-related pathology in mice, which was in line with the findings in our previous study.”
Quote in the paperSubstantial claim - Interpretationown data
The combination of HFD and STZ/I.P. induces an increased inflammatory response in mice.
“suggesting an increased inflammatory response induced by the combination of HFD and STZ/I.P. in mice.”
- Also stated in: § Discussion · hedged
“suggesting an increased inflammatory response induced by the combination of HFD and STZ/I.P. in mice.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Interpretationown data
The combination of high-fat diet and intraperitoneal streptozotocin could promote the activation of microglia and astrocytes in the hippocampus of mice.
“suggesting that combination of HFD and STZ/I.P. could promote the activation of microglia and astrocytes in the hippocampus of mice.”
Quote in the paperSubstantial claim - Interpretationown data
The combination of HFD and STZ/I.P. promotes activation of microglia and astrocytes in the hippocampus of mice.
“indicating that combination of HFD and STZ/I.P. could promote the activation of microglia and astrocytes in the hippocampus of mice.”
Quote in the paperSubstantial claim - Premisecitation
Both T2DM and AD mouse models show a neuroinflammation-related imbalance of TREM1/2 expression in the hippocampus, closely related to impaired behavioral task performance.
“both T2DM and AD mice models showed a neuroinflammation-related imbalance of TREM1/2 expression in the hippocampus, with a close relation with the impaired performance in behavioral tasks (Fan et al., 2022).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Fan et al., 2022 source
- Interpretationreasoning
The mechanism of the induced AD-like dysfunction might involve neuroinflammation and its associated dysfunction of the IRS1/AKT/ERK signaling pathway.
“the mechanism might be involved with neuroinflammation and its associated dysfunction of IRS1/AKT/ERK signaling pathway.”
Quote in the paperSubstantial claim - Interpretationown data
Neuroinflammation plays a crucial role in the pathogenesis of AD.
“Together with the increased activation of microglia and astrocytes, as well as the elevated expression of IL-1β, IL-6, and TNF-α, these results further support the crucial role of neuroinflammation in the pathogenesis of AD.”
- Also stated in: § Discussion · plain
“growing evidence has highlighted the role of neuroinflammation in the pathogenesis and progression of AD (Medeiros et al., 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Medeiros et al., 2010 source
- Also stated in: § Discussion · plain
- Interpretationown data
The combination of high-fat diet and intraperitoneal streptozotocin could induce glucose metabolic turmoil and Alzheimer's disease-like neuropsychiatric dysfunction in mice.
“combination of HFD and STZ/I.P. could induce glucose metabolic turmoil and Alzheimer's disease (AD)-like neuropsychiatric dysfunction in mice, as indicated by the increased concentrations of fasting blood glucose and impaired learning and memory ability.”
- Also stated in: § Significance Statement · hedged
“Our study suggested that combination of HFD and STZ/I.P. could successfully induce AD-like behavioral impairments and neuropathological injuries in mice”
Quote in the paperSubstantial claim- Rests on an assumption: The combination of high-fat diet and intraperitoneal streptozotocin is a widely used and valid method for modeling type 2 diabetes mellitus in mice.
- Rests on an assumption: Impaired performance in the novel object recognition, Y-maze, and Morris water maze tests in mice reflects Alzheimer's disease-like learning and memory dysfunction.
- Also stated in: § Significance Statement · hedged
- Interpretationreasoning
The mechanism of AD-like pathology may be associated with neuron damage and activation of microglia and astrocytes in the hippocampus.
“Apart from the APP accumulation and tau hyperphosphorylation, the mechanism might be associated with neuron damage and activation of microglia and astrocytes in the hippocampus.”
Quote in the paperSubstantial claim - Interpretationown data
The combination of HFD and STZ/I.P. induces AD-like metabolic and behavioral impairments in mice.
“These results suggested that the combined use of HFD and STZ/I.P. could successfully induce AD-like metabolic and behavioral injuries in mice.”
- Also stated in: § Discussion · hedged
“our results showed that combination of HFD and STZ/I.P. could induce not only T2DM-like metabolic disorders but also AD-like neuropsychiatric behavior in mice, as indicated by the increased blood glucose levels and serum insulin levels and the impaired cognitive ability in NOR, Y-maze, and MWM tests.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Interpretationown data
The combination of high-fat diet and intraperitoneal streptozotocin could induce Aβ accumulation and tau hyperphosphorylation in the hippocampus and PFC of mice.
“suggesting that combination of HFD and STZ/I.P. could induce Aβ accumulation and tau hyperphosphorylation in the hippocampus and PFC of mice.”
Quote in the paperSubstantial claim- Rests on an assumption: Increased APP and p-Tau levels indicate Aβ accumulation and tau hyperphosphorylation characteristic of Alzheimer's disease.
- Interpretationown data
The combination of high-fat diet and intraperitoneal streptozotocin could induce potential blood-brain barrier damage in mice.
“suggesting potential BBB damage induced by the combination of HFD and STZ/I.P. in mice (Fig. 3E,F).”
Quote in the paperSubstantial claim- Rests on an assumption: Reduced mRNA expression of ocln, zo-1, and clnds indicates blood-brain barrier damage.
- Interpretationown data
The combination of high-fat diet and intraperitoneal streptozotocin could induce dysregulation of the IRS1/AKT/ERK signaling pathway in the hippocampus and PFC of mice.
“suggesting that combination of HFD and STZ/I.P. could induce the dysregulation of the IRS1/AKT/ERK signaling pathway in the hippocampus and the PFC of mice.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 31
- May combine two claims. 18
- The quote only partly states this claim. 5
Classified as probably not a substantial claim.
PremisecitationTREM2 maintains the phagocytic ability of microglia toward Aβ deposits.
“which has been proven to maintain the phagocytic ability of microglia toward Aβ deposits (Y. Wang et al., 2015; S. Wang et al., 2022).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites Y. Wang et al., 2015 source
The Results section, “TREM2 deficiency affects microglia survival in 5XFAD mice,” reports that TREM2 deficiency had very little effect on microglial uptake or processing of Aβ aggregates and concludes that it does not cause a direct defect in Aβ phagocytosis. The Discussion instead attributes TREM2’s contribution to Aβ removal to sustaining plaque-associated microgliosis, not maintaining the phagocytic ability of individual microglia. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured - cites S. Wang et al., 2022 source
May combine two claims.
PremisecitationImbalance of TREM2 expression is involved in neuronal injury induced by high cholesterol and is related to LPS-induced hyperactivation of microglia and increased secretion of inflammatory factors.
“The results of our previous studies showed that the imbalance of TREM2 expression was not only involved in the process of neuronal injury induced by high cholesterol but also related to LPS-induced hyperactivation of microglia and increased secretion of inflammatory factors (X. R. Gao et al., 2021; Liu et al., 2022; Zheng et al., 2023).”
Quote in the paperSubstantial claim3 of 3 sources checked- cites X. R. Gao et al., 2021 source
The Background reports altered hippocampal TREM2 expression in LPS-challenged rats, and the Results report a TREM1/TREM2 imbalance in high-fat-diet-induced NAFLD rats. The cited paper does not establish TREM2 involvement in neuronal injury specifically induced by high cholesterol, or link its imbalance to LPS-induced microglial hyperactivation and increased inflammatory-factor secretion. The available passages have no page numbers. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites Liu et al., 2022 source
The Discussion and Results describe microglial activation and inflammatory factors in STZ-injected AD-like mice, but do not address TREM2 expression. Searches for TREM2 with high-cholesterol neuronal injury and for LPS-induced microglial hyperactivation found no passage supporting the attributed relationships. Page numbers are unavailable in our copy. (LLM, conf=0.73)
Experimental — accuracy not yet measured - cites Zheng et al., 2023 source
The Discussion (page not provided) reports that high cholesterol injured SH-SY5Y cells, decreased TREM2 expression, and that TREM2 may play a role in those injuries. It does not report LPS-induced microglial hyperactivation or increased secretion of inflammatory factors, so it supports only the cholesterol-injury part of the jointly cited sentence. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation80% of Alzheimer's disease patients also exhibit symptoms of type 2 diabetes mellitus or abnormal glucose and insulin levels.
“80% of AD patients also exhibit symptoms of T2DM or abnormal glucose and insulin levels (S. Gao et al., 2019).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites S. Gao et al., 2019 source
The Introduction reports an association between T2DM and dementia, but gives no estimate of diabetes or abnormal glucose and insulin levels among patients with Alzheimer’s disease. Its 90–95% figure refers to the proportion of diabetes cases that are T2DM, not the claimed 80% of Alzheimer’s patients. Searches for the 80% figure and abnormal glucose or insulin levels in Alzheimer’s patients found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim. May combine two claims.
PremisecitationInsulin resistance affects neuronal function and Aβ accumulation in the brain, contributing to neuroinflammation, synaptic dysfunction, and cognitive decline.
“insulin resistance could affect neuronal function and Aβ accumulation in the brain, which contribute to neuroinflammation and synaptic dysfunction and finally lead to cognitive decline (Arnold et al., 2018).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Arnold et al., 2018 source
The ‘Effects of insulin in neurons’ section describes insulin’s roles in neuronal and synaptic function, and ‘Systemic insulin resistance and ADRDs’ reports animal-model evidence for amyloid-β accumulation. The review also reports associations between abnormal brain insulin signalling and poorer cognition in ‘Brain insulin resistance in ADRD, irrespective of T2DM.’ It does not establish the claimed sequence through neuroinflammation and synaptic dysfunction to cognitive decline; it notes that human evidence linking systemic insulin resistance to amyloid-β pathology is mostly negative. Page numbers were not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationChronic hyperglycemia promotes the formation of advanced glycation end products and oxidative stress.
“It has been reported that chronic hyperglycemia could promote the formation of advanced glycation end products and oxidative stress (Goh and Cooper, 2008; Joubert et al., 2019)”
Quote in the paperNot a substantial claim1 of 2 sources checkedMay combine two claims.
PremisecitationThere is a potential link between AD and insulin resistance, with decreased key insulin signaling proteins and increased insulin resistance markers in the brains of AD mice.
“Recent studies have suggested a potential link between AD and insulin resistance, which exhibits a decreased level of key insulin signaling proteins and an increased level of insulin resistance markers in the brains of AD mice (Craft et al., 1998; Arnold et al., 2018; Kshirsagar et al., 2021).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Craft et al., 1998 source
- cites Arnold et al., 2018 source
The section “Brain insulin resistance in ADRD, irrespective of T2DM” reports reduced insulin-signalling proteins and abnormal markers of insulin resistance in post-mortem brains of people with AD, supporting the proposed link. It does not establish the claimed decreases and increases in the brains of AD mice; the population in the cited passages is human. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites Kshirsagar et al., 2021 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIL-1β is a key proinflammatory cytokine associated with age-related cognitive decline, and synaptic plasticity, learning, and memory are susceptible to IL-1β-induced impairment, particularly in the aging brain.
“IL-1β is the key proinflammatory cytokine associated with age-related cognitive decline, and growing evidence has suggested that synaptic plasticity, learning, and memory are more susceptible to IL-1β–induced impairment, particularly in the aging brain (Prieto et al., 2015).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Prieto et al., 2015 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationKnockdown of TREM2 alleviates neuroinflammation and prevents neurodegeneration of tau pathology in TREM2−/−PS mice compared with wild-type mice.
“the knockdown of TREM2 could alleviate the neuroinflammation and prevent neurodegeneration of tau pathology in TREM2−/−PS mice compared with wild-type mice (Leyns et al., 2017).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Leyns et al., 2017 source
The Results and Discussion report reduced neuroinflammation and attenuated neurodegeneration in TREM2-deficient PS19 mice compared with TREM2-intact PS19 mice. The claim overstates attenuation as prevention and calls a complete TREM2 knockout a knockdown. The comparator was not non-transgenic wild-type mice. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
PremisecitationHippocampal structural abnormalities and neuronal loss are key neuropathological hallmarks of AD, contributing to cognitive decline.
“Research studies have shown that hippocampal structural abnormalities and neuronal loss are the key neuropathological hallmarks of AD, contributing to the cognitive decline observed in the disease (Venkateshappa et al., 2012; Scheltens et al., 2021).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites Venkateshappa et al., 2012 source
- cites Scheltens et al., 2021 source
The Imaging biomarkers section identifies medial temporal lobe atrophy as a validated imaging measure of neurodegeneration in Alzheimer’s disease. The Fluid biomarkers section relates synaptic pathology to cognitive decline. However, the paper identifies amyloid and tau pathology as defining characteristics; it does not establish hippocampal neuronal loss as a key neuropathological hallmark or directly link hippocampal structural changes to cognitive decline. (LLM, conf=0.85)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationImbalance of TREM2 is involved in neuronal injury induced by high cholesterol and is related to LPS-induced homeostatic imbalance of microglia and increased secretion of inflammatory factors.
“The results of our previous studies showed that the imbalance expression of TREM2 was not only involved in the neuronal injury induced by high cholesterol but also related to LPS-induced homeostatic imbalance of microglia and increased secretion of inflammatory factors (Liu et al., 2022; Zheng et al., 2023).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites Liu et al., 2022 source
The Discussion and Results describe microglial activation and elevated inflammatory factors in STZ-injected AD-like mice. Searches for TREM2 with high-cholesterol neuronal injury and for LPS-induced microglial imbalance found no passage addressing either claimed relationship; the broader inflammation findings do not establish them. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites Zheng et al., 2023 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAβ aggregation and excessive phosphorylation of tau impair microtubule stability, affecting axonal transport, leading to neuronal degeneration, synaptic loss, and cognitive impairment in AD.
“Studies have shown that Aβ aggregation and excessive phosphorylation of tau can impair microtubule stability, thereby affecting axonal transport, leading to neuronal degeneration and synaptic loss, and exacerbating the progression of cognitive impairment in AD (Selkoe and Hardy, 2016; Jack et al., 2018).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites Selkoe and Hardy, 2016 source
The section “Connecting plaques and tangles: Aβ can drive tau alteration” (page not available) reports that Aβ oligomers induce tau hyperphosphorylation and neuritic dystrophy. The section “Synaptic loss, Aβ, and amyloid plaques” links Aβ oligomers to synaptic loss and impaired memory. Our copy does not establish the claimed intermediate mechanism of impaired microtubule stability and axonal transport. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Jack et al., 2018 source
Section 15 describes a proposed sequence from amyloid pathology to pathologic tau, neurodegeneration, and cognitive decline; Section 9.4 links synapse loss with AD symptoms. The paper does not describe impaired microtubule stability or axonal transport as steps in that sequence, and it presents the causal sequence as a hypothesis rather than an established mechanism. Page numbers were not provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim. May combine two claims.
PremisecitationIRS1, AKT, and ERK are key components of the insulin signaling pathway; impaired IRS1 signaling leads to decreased activation of AKT and subsequent dysregulation of ERK involved in insulin resistance and metabolic dysfunction.
“Insulin receptor substrate 1 (IRS1), protein kinase B (AKT), and ERK are the key components of the insulin signaling pathway; impaired IRS1 signaling leads to decreased activation of AKT and subsequent dysregulation of ERK involved in insulin resistance and metabolic dysfunction (Ding et al., 2019).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Ding et al., 2019 source
Section 3.3 identifies IRS1 as connecting insulin receptor activation to downstream Akt and ERK pathways, and reports reduced phosphorylation of all three in high-glucose-treated HepG2 cells. The Discussion also describes this as impaired insulin signaling. Neither passage establishes the claimed sequence in which reduced Akt activation subsequently dysregulates ERK. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationGenetic polymorphisms of TREM1/2 are closely associated with the pathogenesis of AD.
“It has been reported that there has a close association between genetic polymorphisms of TREM1/2 and the pathogenesis of AD (Y. Wang et al., 2015).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Y. Wang et al., 2015 source
The Introduction reports that a rare TREM2 R47H mutation is associated with substantially increased AD risk, and the paper examines how TREM2 affects an AD mouse model. The cited passages do not establish an association between TREM1 polymorphisms and AD, so the TREM1/2 claim is broader than the source supports. No page numbers are available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measured
May combine two claims.
Findingown dataBody weight in the model group increased after high-fat diet induction and began to decline upon streptozotocin treatment after 8 weeks, compared with the control group.
“The tendency of the bodyweight in the Mod group was increased after HFD induction and began to decline upon STZ treatment after 8 weeks when compared with the Con group in Figure 1E.”
Quote in the paperNot a substantial claimThe quote only partly states this claim.
Findingown dataIn Mod mice, blood glucose level was significantly increased compared with control mice.
“Consistently, in the present study, our results showed that combination of HFD and STZ/I.P. could induce a significant increase in blood glucose level, serum insulin, and the HOMA-IR index in mice.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataIn Mod mice, serum insulin level was significantly increased compared with control mice.
“Consistently, in the present study, our results showed that combination of HFD and STZ/I.P. could induce a significant increase in blood glucose level, serum insulin, and the HOMA-IR index in mice.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataIn Mod mice, protein expression of p-IRS1/IRS1 was increased in the hippocampus and PFC compared with control mice.
“the results of the present study showed that the protein expression levels of p-IRS1/IRS1 were increased, while the levels of p-AKT/AKT and p-ERK/ERK were decreased in the hippocampus and PFC of mice induced by the combination of HFD and STZ/I.P.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataIn Mod mice, protein expression of p-ERK/ERK was decreased in the hippocampus and PFC compared with control mice.
“the results of the present study showed that the protein expression levels of p-IRS1/IRS1 were increased, while the levels of p-AKT/AKT and p-ERK/ERK were decreased in the hippocampus and PFC of mice induced by the combination of HFD and STZ/I.P.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenmRNA expression does not directly equate to protein function or localization.
“While mRNA expression data provide compelling evidence of potential BBB damage and increased inflammatory response in our model, it is important to note that mRNA expression does not directly equate to protein function or localization.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningAll data points were included in the plots.
“All data points were included in the plots to maintain transparency and facilitate a comprehensive analysis of the results.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.
Study design and conductnone givenThree mice were randomly selected from each group for immunofluorescence and Western blot analyses.
“Three mice were randomly selected from each group, and the hippocampus and the PFC were carefully separated, rapidly frozen in liquid nitrogen, and stored at −80°C.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationSTZ kills pancreatic β-cells and has been widely used to establish T2DM animal models.
“Given the killing effect of STZ on the pancreatic β-cell, it has been widely used in establishing T2DM animal models (Ganda et al., 1976; Grieb, 2016).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Ganda et al., 1976 source
- cites Grieb, 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenThe findings may not be generalizable to female mice.
“It is important to note that the findings may not be generalizable to female mice.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningImbalanced protein expression of the IRS1/AKT/ERK signaling pathway and TREM1/2, as well as increased inflammatory factors, may be involved in the AD-like pathological process.
“Moreover, the imbalanced protein expression of the IRS1/AKT/ERK signaling pathway and TREM1/2, as well as the increased inflammatory factors, may also be involved in AD-like pathological process.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
Interpretationnone givenThe mouse model used in this study may not fully represent the complexity of human AD, and the findings may not directly translate to human patients.
“the mouse model used in this study may not fully represent the complexity of human AD. Animal models could only partially replicate the disease processes seen in humans, and the findings may not directly translate to human patients.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenAfter acclimatization, the mice were randomly divided into a control group fed standard chow and a model group fed a high-fat diet.
“the mice were randomly divided into two groups, including the control group (Con) fed a standard chow diet (3.766 kcal/g) and the model group (Mod) fed a high-fat diet (60% of calories from fat, 5 kcal/g).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe present study only focused on the hippocampus and PFC of mice, and potential changes in other brain regions were not investigated.
“Moreover, the present study only focused on the hippocampus and PFC of mice, and potential changes in other brain regions were not investigated.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPatients with type 2 diabetes mellitus have more than twice the risk of developing late-onset Alzheimer's disease compared with nondiabetic individuals.
“patients with type 2 diabetes mellitus (T2DM) have more than twice the risk of developing late-onset AD compared with nondiabetic individuals (Zhou et al., 2014)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zhou et al., 2014 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe study protocol was approved by the Ethics Committee of Experimental Animals of Anhui Medical University and followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
“The study protocol was approved by the Ethics Committee of Experimental Animals of Anhui Medical University and followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe sample size in the present study was relatively small.
“Thirdly, the sample size in the present study was relatively small, and larger studies with more animals are needed to confirm and validate the findings.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationActivated microglia and an aberrant proinflammatory phenotype contribute to neuronal damage and synaptic dysfunction by releasing cytokines, reactive oxygen species, and other inflammatory mediators, which perpetuate neurodegeneration and exacerbate Alzheimer's disease progression.
“activated microglia (De Strooper and Karran, 2016) and aberrant proinflammatory phenotype contribute to neuronal damage and synaptic dysfunction by releasing cytokines, reactive oxygen species, and other inflammatory mediators, which could perpetuate neurodegeneration and exacerbate the progression of AD (Tang and Le, 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tang and Le, 2016 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThree replicates were conducted for each qPCR analysis.
“Three replicates were conducted for each qPCR analysis, and the data were analyzed using the 2−ΔΔCt method.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningThe Wilcoxon rank-sum test was also conducted to account for potential deviations from normality and small sample size.
“we also conducted the Wilcoxon rank-sum test to account for potential deviations from normality and small sample size.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationTREM2-expressing microglia are found in the peripheral regions of amyloid plaques in APP23 transgenic mice, and increased TREM2 expression is consistent with the progression of amyloid deposition.
“TREM2-expressing microglia cells have been found in the peripheral regions of amyloid plaques in APP23 transgenic (Tg) mice, and increased TREM2 expression is consistent with the progression of amyloid deposition (Frank et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Frank et al., 2008 source
Classified as probably not a substantial claim.
PremisecitationThe most significant pathological changes in Alzheimer's disease are the accumulation of abnormal protein aggregates, primarily Aβ plaques and tau neurofibrillary tangles.
“The most significant pathological changes in Alzheimer's disease are the accumulation of abnormal protein aggregates in the brain, primarily including Aβ plaques and tau neurofibrillary tangles.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scheltens et al., 2016, 2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCombined stimulation of IL-1β, IL-6, and IFN-γ induces APP production and increased Aβ levels.
“combined stimulation of IL-1β, IL-6, and IFN-γ in U373 glioblastoma cell lines and primary human astrocytes could induce APP production and lead to increased Aβ levels (Blasko et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Blasko et al., 2000 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationReactive microglia and astrocytes promote neuroinflammation by releasing cytokines and inflammatory factors such as IL-1β and IL-6 in AD.
“Reactive microglia and astrocytes could promote neuroinflammation by releasing cytokines and inflammatory factors such as IL-1β and IL-6 in AD (H. S. Hong et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites H. S. Hong et al., 2003 source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationActivated AKT and ERK are major kinases for tau phosphorylation and APP deposition in AD, and brain insulin resistance induces decreased phosphorylation levels of AKT and ERK.
“activated AKT and ERK were also suggested to be the major kinase for tau phosphorylation and APP deposition in AD, and the brain insulin resistance emerging in AD further induces the decreased phosphorylation levels of AKT and ERK (Oliveira et al., 2021).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Oliveira et al., 2021 source
Classified as probably not a substantial claim.
PremisecitationMap-2 and NeuN are widely used to mark mature neurons and neuronal nuclei in the brain.
“The microtubule-associated protein 2 (Map-2) and neuronal nuclei (NeuN) are widely used in marking the mature neurons and neuronal nuclei in the brain (Götz and Ittner, 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Götz and Ittner, 2008 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationKnocking out TREM1 in APP/PSEN1 mice increases Aβ1-42 levels and total amyloid plaque burden, and selective overexpression or activation of TREM1 on microglia improves Aβ neuropathology and rescues AD-related spatial cognitive impairments.
“Knocking out TREM1 in the brains of APP/PSEN1 mice has been shown to increase Aβ1–42 levels and total amyloid plaque burden, and selective overexpression or activation of TREM1 on microglia cells could improve Aβ neuropathology and rescue AD-related spatial cognitive impairments (Jiang et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jiang et al., 2016 source
The paper relies on this without support.
The combination of high-fat diet and intraperitoneal streptozotocin is a widely used and valid method for modeling type 2 diabetes mellitus in mice.
“combination of HFD and STZ/I.P., a widely used T2DM modeling method, could successfully induce AD-like behavioral impairments and neuropathological injuries in mice”
The paper relies on this without support.
Impaired performance in the novel object recognition, Y-maze, and Morris water maze tests in mice reflects Alzheimer's disease-like learning and memory dysfunction.
“as indicated by the increased concentrations of fasting blood glucose and impaired learning and memory ability.”
The paper relies on this without support.
Reduced mRNA expression of ocln, zo-1, and clnds indicates blood-brain barrier damage.
“suggesting potential BBB damage induced by the combination of HFD and STZ/I.P. in mice (Fig. 3E,F).”
The paper relies on this without support.
Increased APP and p-Tau levels indicate Aβ accumulation and tau hyperphosphorylation characteristic of Alzheimer's disease.
“suggesting that combination of HFD and STZ/I.P. could induce Aβ accumulation and tau hyperphosphorylation in the hippocampus and PFC of mice.”
The paper relies on this without support.
Findings in this mouse model can inform the pathophysiology of the comorbidity of type 2 diabetes mellitus and Alzheimer's disease in humans.
“Our findings further support the potential overlap between T2DM and AD pathophysiology, providing insight into the mechanisms underlying the comorbidity of these diseases.”
The paper relies on this without support.
The effects observed in Mod mice are attributable to the combination of HFD and STZ/I.P., rather than to either treatment alone.
“These results suggested that the combined use of HFD and STZ/I.P. could successfully induce AD-like metabolic and behavioral injuries in mice.”
The paper relies on this without support.
The mouse model used in this study adequately represents human AD for the purpose of the conclusions drawn.
“These results indicated that combination of HFD and STZ/I.P. could induce an AD-related pathology in mice, which was in line with the findings in our previous study.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Abstract reverses the direction of BBB-marker changes
MajorThe abstract says ocln, zo-1, and clnds increased in model mice, whereas the Results say all three were reduced in both the hippocampus and PFC. The direction matters to the paper's interpretation of blood-brain barrier damage.
“the model mice presented increased levels of APP, p-Tau, p-IRS1, TREM2, IL-1β, IL-6, TNF-α, ocln, zo-1, and clnds”
“the mRNA expression levels of ocln, zo-1, and clnds in the hippocampus and PFC of Mod mice were all remarkably reduced compared with the Con ones”
Figure 4E identifies the colocalized protein inconsistently
MinorThe Results describe Figure 4E as colocalization of APP with a neuronal marker, but the figure caption calls it colocalization of Aβ with neurons. APP and Aβ are different molecules.
“We also conducted a colocalization of APP and neuronal marker (Fig. 4E).”
“E, The colocalization of Aβ with neurons.”
Cites
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465 · see citing works
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · cited 1× · see citing works
“Inrecent years, growing evidence highlighted the role of microglia and its related neu-roin fl ammation in the pathogenesis and progression of AD (S. Hong et al., 2016; Hansen et al., 2018).”
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125 · see citing works
Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · see citing works
Microglia and macrophages in brain homeostasis and disease
Li, Q., & Barres, B. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.125 · Cited by 1,999 · see citing works
The Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990 · see citing works
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · see citing works
Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures
Cummings, J. L., Morstorf, T., & Zhong, K. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt269 · Cited by 1,744 · see citing works
TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736 · see citing works
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Microglia Biology: One Century of Evolving Concepts
Prinz, M., Jung, S., & Priller, J. (2019) · Cell · doi:10.1016/j.cell.2019.08.053 · Cited by 1,525 · see citing works
Interplay of Hippocampus and Prefrontal Cortex in Memory
Preston, A. R., & Eichenbaum, H. (2013) · Current Biology · doi:10.1016/j.cub.2013.05.041 · Cited by 1,389 · see citing works
Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline
Bussian, T. J., Aziz, A., Meyer, C. F., Swenson, B. L., van Deursen, J. M., & Baker, D. J. (2018) · Nature · doi:10.1038/s41586-018-0543-y · Cited by 1,289 · see citing works
Rajan, K. B., Weuve, J., Barnes, L. L., McAninch, E. A., Wilson, R. S., & Evans, D. A. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12362 · Cited by 1,268 · see citing works
Mfsd2a is critical for the formation and function of the blood-brain barrier
Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B. J., Mayshar, Y., Yan, H., & Gu, C. (2014) · Nature · doi:10.1038/nature13324 · Cited by 1,037 · see citing works
The Role of Advanced Glycation End Products in Progression and Complications of Diabetes
Goh, S.-Y., & Cooper, M. E. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1817 · Cited by 987 · see citing works
Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology
Ashton, N. J., Brum, W. S., Di Molfetta, G., Benedet, A. L., Arslan, B., Jonaitis, E., Langhough, R. E., Cody, K., Wilson, R., Carlsson, C. M., et al. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2023.5319 · Cited by 884 · cited 1× · see citing works
“Moreover, increasing data suggested a close relation between metabolic disorders, especially diabetes mellitus, and the development of AD (Chakrabarti et al., 2015; Ashton et al., 2024).”
The myeloid cells of the central nervous system parenchyma
Ransohoff, R. M., & Cardona, A. E. (2010) · Nature · doi:10.1038/nature09615 · Cited by 804 · see citing works
Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello, C., Yuan, P., Schain, A., & Grutzendler, J. (2015) · Nature Communications · doi:10.1038/ncomms7176 · Cited by 718 · see citing works
Hyperinsulinemia and risk of Alzheimer disease
Luchsinger, J. A., Tang, M.-X., Shea, S., & Mayeux, R. (2004) · Neurology · doi:10.1212/01.wnl.0000140292.04932.87 · Cited by 683 · see citing works
Animal models of Alzheimer's disease and frontotemporal dementia
Götz, J., & Ittner, L. M. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2420 · Cited by 676 · see citing works
Drug treatments in Alzheimer’s disease
Briggs, R., Kennelly, S. P., & O’Neill, D. (2016) · Clinical Medicine · doi:10.7861/clinmedicine.16-3-247 · Cited by 571 · see citing works
Craft, S., Peskind, E., Schwartz, M. W., Schellenberg, G. D., Raskind, M., & Porte, D. (1998) · Neurology · doi:10.1212/wnl.50.1.164 · Cited by 560 · see citing works
Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710311114 · Cited by 517 · see citing works
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.033 · Cited by 471 · see citing works
Sosna, J., Philipp, S., Albay, R., Reyes-Ruiz, J. M., Baglietto-Vargas, D., LaFerla, F. M., & Glabe, C. G. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0244-x · Cited by 406 · see citing works
Microtubule-associated protein tau in development, degeneration and protection of neurons
Wang, J., & Liu, F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.03.002 · Cited by 395 · see citing works
Mechanisms of sex differences in Alzheimer’s disease
Lopez-Lee, C., Torres, E. R. S., Carling, G., & Gan, L. (2024) · Neuron · doi:10.1016/j.neuron.2024.01.024 · Cited by 376 · see citing works
Grieb, P. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9132-3 · Cited by 362 · see citing works
Liu, S., Fan, M., Xu, J.-X., Yang, L.-J., Qi, C.-C., Xia, Q.-R., & Ge, J.-F. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02393-2 · Cited by 296 · see citing works
Self-citationAging and Alzheimer's disease pathology
Sengoku, R. (2019) · Neuropathology · doi:10.1111/neup.12626 · Cited by 289 · see citing works
Blasko, I., Veerhuis, R., Stampfer-Kountchev, M., Saurwein-Teissl, M., Eikelenboom, P., & Grubeck-Loebenstein, B. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0321 · Cited by 258 · see citing works
Ding, X., Jian, T., Wu, Y., Zuo, Y., Li, J., Lv, H., Ma, L., Ren, B., Zhao, L., Li, W., et al. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.018 · Cited by 258 · see citing works
Diabetes and Alzheimer’s disease crosstalk
Baglietto‐Vargas, D., Shi, J. J., Yaeger, D. M., Ager, R. R., & LaFerla, F. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.005 · Cited by 254 · see citing works
TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice
Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I., & Deller, T. (2008) · Glia · doi:10.1002/glia.20710 · Cited by 247 · see citing works
Venkateshappa, C., Harish, G., Mahadevan, A., Srinivas Bharath, M. M., & Shankar, S. K. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0755-8 · Cited by 232 · see citing works
Ghatak, S., Dolatabadi, N., Trudler, D., Zhang, X., Wu, Y., Mohata, M., Ambasudhan, R., Talantova, M., & Lipton, S. A. (2019) · eLife · doi:10.7554/elife.50333 · Cited by 227 · see citing works
Studies on Streptozotocin Diabetes
Ganda, O. P., Rossini, A. A., & Like, A. A. (1976) · Diabetes · doi:10.2337/diab.25.7.595 · Cited by 224 · see citing works
Type 2 Diabetes and Cognitive Function in Community-Dwelling Elderly Women
Grodstein, F., Chen, J., Wilson, R. S., & Manson, J. E. (2001) · Diabetes Care · doi:10.2337/diacare.24.6.1060 · Cited by 223 · see citing works
Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
Tay, T. L., Béchade, C., D’Andrea, I., St‐Pierre, M., Henry, M. S., Roumier, A., & Tremblay, M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00421 · Cited by 211 · see citing works
Systemic Catabolism of Alzheimer's Aβ40 and Aβ42
Ghiso, J., Shayo, M., Calero, M., Ng, D., Tomidokoro, Y., Gandy, S., Rostagno, A., & Frangione, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407668200 · Cited by 209 · see citing works
Tau deletion promotes brain insulin resistance
Marciniak, E., Leboucher, A., Caron, E., Ahmed, T., Tailleux, A., Dumont, J., Issad, T., Gerhardt, E., Pagesy, P., Vileno, M., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20161731 · Cited by 205 · see citing works
APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints
Yin, Z., Rosenzweig, N., Kleemann, K. L., Zhang, X., Brandão, W., Margeta, M. A., Schroeder, C., Sivanathan, K. N., Silveira, S., Gauthier, C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01627-6 · Cited by 202 · cited 1× · see citing works
“Speci fi cally, microglial activation attempts to eliminate A β accumulation by phagocytosis and clearance (Yin et al., 2023); however, the generation and accumulation of A β could cause microglial dysfunction by releasing the in fl ammatory mediators (Sosna et al., 2018).”
Rad, S. K., Arya, A., Karimian, H., Madhavan, P., Rizwan, F., Koshy, S., & Prabhu, G. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s173970 · Cited by 158 · see citing works
Chakrabarti, S., Kumar Khemka, V., Banerjee, A., Chatterjee, G., Ganguly, A., & Biswas, A. (2015) · Aging and disease · doi:10.14336/ad.2014.002 · Cited by 134 · see citing works
Prieto, G. A., Snigdha, S., Baglietto-Vargas, D., Smith, E. D., Berchtold, N. C., Tong, L., Ajami, D., LaFerla, F. M., Rebek, J., & Cotman, C. W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514486112 · Cited by 126 · see citing works
Medeiros, R., Figueiredo, C. P., Pandolfo, P., Duarte, F. S., Prediger, R. D. S., Passos, G. F., & Calixto, J. B. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.01.040 · Cited by 121 · see citing works
Structure and mechanism of blood–brain-barrier lipid transporter MFSD2A
Wood, C. A. P., Zhang, J., Aydın, D., Xu, Y., Andreone, B. J., Langen, U. H., Dror, R. O., Gu, C., & Feng, L. (2021) · Nature · doi:10.1038/s41586-021-03782-y · Cited by 106 · see citing works
TREM1 facilitates microglial phagocytosis of amyloid beta
Jiang, T., Zhang, Y.-D., Gao, Q., Zhou, J.-S., Zhu, X.-C., Lu, H., Shi, J.-Q., Tan, L., Chen, Q., & Yu, J.-T. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1622-5 · Cited by 91 · see citing works
Interferon γ stimulates β-secretase expression and sAPPβ production in astrocytes
Hong, H. S., Hwang, E. M., Sim, H. J., Cho, H.-J., Boo, J. H., Oh, S. S., Kim, S. U., & Mook-Jung, I. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01270-1 · Cited by 81 · see citing works
Joubert, M., Manrique, A., Cariou, B., & Prieur, X. (2019) · Diabetes & Metabolism · doi:10.1016/j.diabet.2018.07.003 · Cited by 81 · see citing works
Insulin resistance: a connecting link between Alzheimer's disease and metabolic disorder
Kshirsagar, V., Thingore, C., & Juvekar, A. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-020-00622-2 · Cited by 66 · see citing works
Zhou, X., Zhang, J., Chen, Y., Ma, T., Wang, Y., Wang, J., & Zhang, Z. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132354 · Cited by 64 · see citing works
Metformin prevents p-tau and amyloid plaque deposition and memory impairment in diabetic mice
Oliveira, W. H., Braga, C. F., Lós, D. B., Araújo, S. M. R., França, M. R., Duarte-Silva, E., Rodrigues, G. B., Rocha, S. W. S., & Peixoto, C. A. (2021) · Experimental Brain Research · doi:10.1007/s00221-021-06176-8 · Cited by 64 · see citing works
Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model
Chen, W., Huang, Q., Lazdon, E., Gomes, A., Wong, M., Stephens, E. R., Royal, T. G., Frenkel, D., Cai, W., & Kahn, C. R. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2220684120 · Cited by 60 · see citing works
Qi, C., Chen, X.-X., Gao, X., Xu, J., Liu, S., & Ge, J. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.633495 · Cited by 52 · see citing works
Self-citationFan, M., Liu, S., Sun, H.-M., Ma, M.-D., Gao, Y.-J., Qi, C.-C., Xia, Q.-R., & Ge, J.-F. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113375 · Cited by 50 · see citing works
Self-citationGao, X.-R., Chen, Z., Fang, K., Xu, J.-X., & Ge, J.-F. (2021) · Lipids in Health and Disease · doi:10.1186/s12944-021-01590-x · Cited by 47 · see citing works
Self-citationGao, S., Chen, Y., Sang, F., Yang, Y., Xia, J., Li, X., Zhang, J., Chen, K., & Zhang, Z. (2019) · Diabetes · doi:10.2337/db19-0233 · Cited by 46 · see citing works
Maldonado‐Díaz, C., Hiya, S., Yokoda, R. T., Farrell, K. W., Marx, G. A., Kauffman, J., Daoud, E. V., Gonzales, M. M., Parker, A. S., Canbeldek, L., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02716-y · Cited by 36 · see citing works
Gao, X., Wei, Y.-D., Sun, H., Hao, S., Ma, M.-D., Sun, H., Zang, D., Qi, C., & Ge, J. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03360-5 · Cited by 23 · see citing works
Self-citationGao, X., Sun, H., Hao, S., Sun, H., & Ge, J. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115846 · Cited by 15 · see citing works
Self-citationZheng, Q., Han, Y., Fan, M., Gao, X., Ma, M., Xu, J., Liu, S., & Ge, J. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.11904 · Cited by 6 · see citing works
Self-citationDirect conversion of fibroblast into neurons for Alzheimer's disease research: a systematic review
Sattarov, R., Toresson, H., Orbjörn, C., & Mattsson-Carlgren, N. (2023) · Journal of Alzheimer’s Disease · doi:10.3233/jad-230119 · Cited by 4 · see citing works
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Adak, S., Singh, S., Jain, R., Tiwari, A., Singh, B., Kumar, S., Dadhwal, A., Chakroborty, A., Sharma, A. K., Singh, R. P., et al. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1646551 · Cited by 9 · see citing works
Seong, K.-J., Lee, S., Lee, J. H., Ko, H.-M., Nam, T., Kim, T.-Y., Choi, W., Jung, J., & Kim, W.-J. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05473-5 · Cited by 4 · see citing works
Seong, K.-J., Mun, B.-R., Kim, S., Choi, W., Lee, S. J., Jung, J., & Kim, W.-J. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123490 · Cited by 4 · see citing works
Fang, J., Zhang, X., Qi, Z., Zhou, L., Chen, Y., Li, Q., Liu, R., & Yu, H. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1580775 · Cited by 3 · see citing works
Zhang, D., Sheng, J., He, P., Wang, J., zhou, M., Sun, Y., Cao, Y., Jiang, Y., Jia, H., Wang, L., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1794560 · Cited by 2 · see citing works
Cheng, M., Zheng, X., Wei, Y.-D., & Ge, J. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179152 · Cited by 1 · see citing works
Self-citationMeng, X., Liu, Z., Zhao, Z., Chen, L., Li, S., Qi, S., Guo, R., Zhang, X., Meng, F., Zhang, H., et al. (2026) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-01313
Aranđelović-Ilić, J., & Djuretić, J. (2026) · Arhiv za farmaciju · doi:10.5937/arhfarm76-64833
Kawaharada, R., Kimura, R., Miyata, E., Noguchi, R., Toriumi, A., & Nakamura, A. (2026) · Nutrients · doi:10.3390/nu18111748
Xing, S., Ren, P., Chen, Z., & Fu, Y. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.07.063
Sun, H., Gao, X., Xu, Q., Chen, F., Xu, M., & Ge, J. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2026.168412
Self-citationDeng, Q., Gao, S., Xue, S.-G., Zhang, S.-Q., Yang, J., Cui, Q., Zhang, C., & Zhou, H.-Y. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108446
- Authors
- Sun, H., Gao, X., Niu, J., Chen, P., He, S., Xu, S., & Ge, J.
- Affiliations
- Anhui Medical University (CN)
- Venue
- eneuro
- Publisher
- Society for Neuroscience
- Published
- 2024-12
- Volume
- 11
- Issue
- 12
- Pages
- ENEURO.0310-24.2024
- ISSN
- 2373-2822 (ISSN-L)
- PMC
- PMC11653102
- OpenAlex
- W4404955622
- Semantic Scholar
- b287dee10d1aa7ee1be9d247723ada452a901d72
- Cited by
- 12
- References
- 66
- Citations by year
- 2026: 8 · 2025: 4
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- eNeuro (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National natural science foundation of china (81870413)
- Scientific Research Promotion Plan of Anhui Medical University (2022xkjT009)
- Anhui Province Postgraduate Education Quality Project (2023xscx050)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, type 2 diabetes, high-fat diet, streptozotocin, learning and memory impairment, neuroinflammation, blood-brain barrier, glycolipid metabolism, comorbidities, hippocampus
- MeSH terms
- Alzheimer Disease, Animals, Blood Glucose, Disease Models, Animal, Hippocampus, Male, Mice, Inbred C57BL, Streptozocin, Mice, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-02.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-02.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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