Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders

Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are unclear. Lipoproteins carry most of the circulating oxylipins. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Alterations in plasma lipoprotein oxylipin composition can directly impact inflammatory responses of lipoprotein metabolizing cells. Similar investigations of CNS lipoprotein oxylipins are non-existent to date. However, as APOE4 is associated with Alzheimer's disease-related microglia dysfunction and oxylipin dysregulation, ApoE4-dependent lipoprotein oxylipin modulation in neurological pathologies is suggested. Such investigations are crucial to bridge knowledge gaps linking oxylipin- and lipoprotein-related disorders in both periphery and CNS. Here, after providing a summary of existent literatures on lipoprotein oxylipin analysis methods, we emphasize the importance of lipoproteins in oxylipin transport and argue that understanding the compartmentalization and distribution of lipoprotein oxylipins may fundamentally alter our consideration of the roles of lipoprotein in cardiometabolic and neurological disorders

Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease

Inflammation is an important factor in Alzheimer's disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman's correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer's Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman's correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention

Peripheral inflammation is associated with structural brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease

ABSTRACT Mounting evidence points towards inflammation as an important factor in Alzheimer’s disease (AD) pathogenesis. In this study, we investigated the relationship between a key marker of inflammation – glycoprotein acetyls (GlycA) – in blood and cognitive and brain structural changes in over 1500 participants enrolled into the Alzheimer’s Disease Neuroimaging Initiative. We evaluated those associations cross-sectionally at baseline, followed by an evaluation of whether baseline GlycA can inform about future disease progression. Our results support the following findings: 1) GlycA is elevated in participants diagnosed with AD compared to cognitively normal participants; 2) GlycA level correlates negatively with regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD; 3) baseline GlycA level is associated with executive function decline at 3-9 year follow-up in both male and female participants diagnosed with LMCI at baseline; and 4) baseline GlycA is associated with decline in entorhinal cortex volume at years 2, 4 and 6-8 of follow-up in both male and female participants diagnosed with LMCI at baseline. In conclusion, peripheral inflammation was found to be positively associated with AD diagnosis and future decline in cognition and regional brain volumes. However, we note that the cross-sectional relationship between peripheral inflammation and AD-related brain atrophy is specific to sex and diagnostic status. Our findings point to peripheral inflammation as a risk factor in AD development, which enables the identification of potential markers and therapeutic intervention for participants who are at risk

Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease

Inflammation is an important factor in Alzheimer’s disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman’s correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer’s Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman’s correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3–9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.</p

Polydopamine-Assisted Surface Modification for Bone Biosubstitutes

Polydopamine (PDA) prepared in the form of a layer of polymerized dopamine (DA) in a weak alkaline solution has been used as a versatile biomimetic surface modifier as well as a broadly used immobilizing macromolecule. This review mainly discusses the progress of biomaterial surface modification inspired by the participation of PDA in bone tissue engineering. A comparison between PDA-assisted coating techniques and traditional surface modification applied to bone tissue engineering is first presented. Secondly, the chemical composition and the underlying formation mechanism of PDA coating layer as a unique surface modifier are interpreted and discussed. Furthermore, several typical examples are provided to evidence the importance of PDA-assisted coating techniques in the construction of bone biosubstitutes and the improvement of material biocompatibility. Nowadays, the application of PDA as a superior surface modifier in multifunctional biomaterials is drawing tremendous interests in bone tissue scaffolds to promote the osteointegration for bone regeneration

Pro-resolving Lipid Mediators Within Brain Esterified Lipid Pools are Reduced in Female Rats Chronically Exposed to Traffic-Related Air Pollution or Genetically Susceptible to Alzheimer’s Disease Phenotype

Traffic-related air pollution (TRAP) is a risk factor for Alzheimer’s disease (AD) where neuroinflammation underlies disease progression and pathogenesis. Unresolved inflammation in AD is known to be exacerbated by brain deficits in unesterified pro-resolving lipid mediators enzymatically synthesized from polyunsaturated fatty acids. Recently, we reported that in the brain, unesterified pro-resolving lipid mediators which are bioactive, can also be supplied from less bioactive esterified lipid pools such as neutral lipids (NLs) and phospholipids (PLs). It is not known whether esterified pro-resolving lipid mediators are affected by AD pathology and exacerbated by TRAP exposure. In the present study we addressed this data gap using TgF344-AD male and female rats that express human AD risk genes and their wildtype littermates exposed to filtered air (FA) or TRAP from 1 to 15 months of age. Esterified lipid mediators within NLs and PLs were quantified by mass-spectrometry. We observed a significant reduction in pro-resolving lipid mediators in both NLs and PLs of female TgF344-AD rats compared to wildtype controls. TRAP exposure also reduced pro-resolving lipids in the female brain, mainly in PL pools, but did not exacerbate changes observed in TgF344-AD rats. Minimal changes were observed in males. Our findings indicate that AD genotype and chronic TRAP exposure result in sex-specific deficits in brain esterified pro-resolving lipid mediators, the pool that supplies free and bioactive lipid mediators. These data provide new information on lipid-mediated mechanisms regulating impaired inflammation resolution in AD, and show for the first time that chronic TRAP exposure targets the same lipid network implicated in AD

Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer's disease

Inflammation is an important factor in Alzheimer’s disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman’s correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer’s Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman’s correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3–9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention