Uncovering mechanisms of brain inflammation in Alzheimer's disease with <i>APOE4</i>: Application of single cell‐type lipidomics

Asante, Isaac; Louie, Stan G.; Yassine, Hussein N.

doi:10.1111/nyas.14907

Cited by 7 publications

(2 citation statements)

References 291 publications

(511 reference statements)

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“…20,21) Some secreted factors are known to affect the lipid composition of the brain. [22][23][24] Among those factors, a secreted glycoprotein Reelin contributes to increased levels of polyunsaturated fatty acids in neurons, 23) which may partly explain why Reelin induces dendrite elongation. [25][26][27] However, how neurons regulate plasma membrane polarity is not understood.…”

Section: Discussionmentioning

confidence: 99%

The Plasma Membrane Polarity Is Higher in the Neuronal Growth Cone than in the Cell Body of Hippocampal and Cerebellar Granule Neurons

Oya,

Korogi,

Kohno

et al. 2023

Biological & Pharmaceutical Bulletin

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The polarity of the biological membrane, or lipid order, regulates many cellular events. It is generally believed that the plasma membrane polarity is regulated according to cell type and function, sometimes even within a cell. Neurons have a variety of functionally specialized subregions, each of which bears distinct proteins and lipids, and the membrane polarity of the subregions may differ accordingly. However, no direct experimental evidence of it has been presented to date. In the present study, we used a cell-impermeable solvatochromic membrane probe NR12A to investigate the local polarity of the plasma membrane of neurons. Both in hippocampal and cerebellar granule neurons, growth cones have higher membrane polarity than the cell body. In addition, the overall variation in the polarity value of each pixel was greater in the growth cone than in cell bodies, suggesting that the lateral diffusion and/or dynamics of the growth cone membrane are greater than other parts of the neuron. These tendencies were much less notably observed in the lamellipodia of a non-neuronal cell. Our results suggest that the membrane polarity of neuronal growth cones is unique and this characteristic may be important for its structure and function.

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Section: Discussionmentioning

confidence: 99%

The Plasma Membrane Polarity Is Higher in the Neuronal Growth Cone than in the Cell Body of Hippocampal and Cerebellar Granule Neurons

Oya,

Korogi,

Kohno

et al. 2023

Biological & Pharmaceutical Bulletin

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“…cholesterol in the brain in the case of AD(Jabeen, K et al 2022). Additionally, APOE isoforms, especially ε4, in uence in ammatory markers, such as CRP leading to heightened in ammation(Asante, I. et al 2022). The interplay between APOE gene polymorphism, lipid abnormalities, and in ammation connects the risk of both CVD and AD).In the case of CVD, atherosclerosis plays a signi cant role(Frąk, W. et al 2022).…”

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confidence: 99%

Association of APOE polymorphisms with serological lipid and inflammatory markers

Krishnamurthy,

Rajavelu,

Reddy

et al. 2023

Preprint

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Background The study aims to assess the association of apolipoprotein E (APOE) gene polymorphisms with serological lipid and inflammatory markers to determine their potential role in predicting the risk of cardiovascular diseases (CVD) and Alzheimer's disease (AD). Methods A total of 915 individuals underwent testing for lipid and inflammatory biomarkers at Vibrant America Clinical Laboratory. Clinical data, blood lipid and inflammatory profiles, and APOE genotyping were analyzed using PCR-RFLP. Result Compared to the E3/E3 genotype, individuals with E2/E3 genotypes showed higher levels of HDL, triglycerides, APOA, HSCRP, and MPO. E2/E4 genotype carriers had higher levels of HDL, triglycerides, Lp(a), and BNPNT. E3/E4 genotypes were associated with elevated levels of total cholesterol, LDL, Lp(a), HSCRP, SDLDL, OXLDL, MPO, LDL-CAL, PLAC, and APOB. The E4/E4 group displayed higher concentrations of total cholesterol, LDL cholesterol, APOB, Lp(a), HSCRP, SDLDL, OXLDL, MPO, LDLCAL, and PLAC compared to E3/E3 carriers. These findings highlight the atherogenic effect of the ε4 allele and the potential protective effect of the ε2 allele on lipid and inflammatory markers. Conclusion This study provides strong evidence linking APOE gene polymorphism to abnormal serum lipid and inflammatory profiles. Individuals carrying the e4 alleles exhibited dysregulated lipid metabolism and abnormal inflammatory markers, increasing their risk of CVD and AD. Early detection and prompt diagnosis are crucial for implementing therapeutic, dietary, and lifestyle interventions to mitigate risks and prevent or delay lipid and inflammation-related disorders.

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Diagnostic Value of Serum Apolipoprotein B100 Combined With Hippocampal Volume in Alzheimer's Disease

Zhang,

Wu,

Ren

et al. 2024

Brain and Behavior

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PurposeTo explore the diagnostic value of serum apolipoprotein B100 (Apo B100) combined with hippocampal volume in Alzheimer's disease (AD).MethodsA total of 59 AD patients and 59 healthy subjects were selected. The Mini‐Mental State Examination (MMSE) was used for neuropsychological assessment. Blood glucose and serum lipid levels were detected by biochemical analyzer. Polymerase chain reaction (PCR) was used to detect apolipoprotein E (Apo E) ε3/ε4 genotypes in the plasma. Hippocampal volume was calculated using Slicer software. Independent‐sample t test or Mann–Whitney U test were used to compare the levels of various indicators between the two groups. Spearman's correlation analysis was used to analyze the correlation between each level. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to compare the diagnostic efficacy of individual and combined detection of serum Apo B100 levels and hippocampal volume in AD.ResultsCompared with the healthy control group, the levels of serum total cholesterol (TC), low‐density lipoprotein (LDL), Apo B100, and plasma Apo E ε3/ε4 were higher in the AD group, and serum high‐density lipoprotein (HDL) level was lower in the AD group (both p < 0.05). The hippocampal volume in the AD group was lower than in the control group (p < 0.01). The serum Apo B100 level was negatively correlated with MMSE score (r = −0.646), whereas hippocampal volume was positively correlated with MMSE score (r = 0.630). ROC curve analysis showed that the AUC of the combined serum Apo B100 level and hippocampal volume for AD was higher than that of either alone (AUC = 0.821, p < 0.01).ConclusionSerum Apo B100 level is elevated, and the hippocampal volume is reduced in AD patients. The combined detection of the two has a higher diagnostic efficiency for AD than other alone and has the potential to become an important indicator for the diagnosis of AD in the future.

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Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell‐type lipidomics

Cited by 7 publications

References 291 publications

The Plasma Membrane Polarity Is Higher in the Neuronal Growth Cone than in the Cell Body of Hippocampal and Cerebellar Granule Neurons

The Plasma Membrane Polarity Is Higher in the Neuronal Growth Cone than in the Cell Body of Hippocampal and Cerebellar Granule Neurons

Association of APOE polymorphisms with serological lipid and inflammatory markers

Diagnostic Value of Serum Apolipoprotein B100 Combined With Hippocampal Volume in Alzheimer's Disease

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