Peripheral versus central nervous system APOE in Alzheimer’s disease: Interplay across the blood-brain barrier

Chernick, Dustin; Ortiz-Valle, Stephanie; Jeong, Angela; Qu, Wenhui; L, Li

doi:10.1016/j.neulet.2019.134306

Cited by 46 publications

(41 citation statements)

References 158 publications

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“…A recent study has found that microglia and the activation of NLRP3 inflammasome are vital for the pathogenesis of AD in tau, which supports the amyloid-cascade hypothesis of AD (Ising et al, 2019). Besides, cholesterol exerts an essential influence in plasma membrane regionalization, signal transduction, myelin sheath formation, and synaptic formation and maintenance (Chernick et al, 2019). Peripheral blood cholesterols can affect the human brain and AD through the blood-brain barrier (BBB) (Gamba et al, 2019).…”

Section: Discussionmentioning

confidence: 77%

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Tang

Wang

Yang

et al. 2020

Front. Aging Neurosci.

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Objectives: Blood lipid profiles have been ambiguously reported as biomarkers of AD in recent years. This study was conducted to evaluate the correlation between blood lipid levels and AD in later-life and to explore the effectiveness and reliability of blood lipid profiles as biomarkers of AD. Methods: Database searching was conducted using PubMed, the Cochrane Library, EMBASE, and Medline. This study was designed following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria. Review Manager 5.3 (RevMan 5.3) software was adopted to perform meta-analysis evaluating the standard mean difference (SMD) with its 95% confidence intervals (CI). Results: A total of 5,286 participants were enrolled from 27 case-control studies in this meta-analysis. The pooled results demonstrated that total cholesterol (TC) level was significantly associated with AD in late-life (SMD = 0.17, 95% CI: [0.01, 0.32], P = 0.03), especially in the subgroup under 70 years old (SMD: 0.45, 95% CI: [0.11, 0.79], P = 0.01) and the subgroup of Western population (SMD: 0.29, 95% CI: [0.04, 0.53], P = 0.02). In the subgroup under 70 years old, the high-density lipoprotein cholesterol (HDL-C) level (SMD = −0.50, 95% CI: [−0.76, −0.25], P = 0.0001) and the low-density lipoprotein cholesterol (LDL-C) level (SMD = 0.59, 95% CI: [0.02, 1.16], P = 0.04) in the AD group were significantly lower and higher than in the control group, respectively. In the subgroup with a sample size larger than 100 subjects, the LDL-C level was significantly higher in AD patients than in the control elderly group (SMD = 0.31, 95% CI: [0.05, 0.56], P = 0.02). There was no significant association between triglyceride (TG) levels and AD in later-life (SMD = −0.00, 95% CI: [−0.12, 0.12], P = 1.00). Tang et al. Association Between Lipids and AD Conclusion: TC can be a new predictive biomarker of AD or cognitive decline in later-life. Increased TC levels are found to be associated with an elevated risk of AD. Decreased HDL-C levels and increased LDL-C levels may relate to an elevated risk of AD in subjects aged 60-70. Further comprehensive researches will be necessary in the future.

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Section: Discussionmentioning

confidence: 77%

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Tang

Wang

Yang

et al. 2020

Front. Aging Neurosci.

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“…Unlike APOA-I, which is produced primarily in the periphery and only limitedly reaches the CNS by crossing the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB) at choroid plexus [22][23][24], APOE is the main APO in the brain. Notably, APOE in the periphery does not cross the BBB and thus, APOE in the brain is exclusively synthesized locally, predominantly by astrocytes, and forms HDL-like particles [25]. APOE exists in three isoforms in human: APOE2, APOE3, and APOE4 with the APOE3 being the most prevalent.…”

Section: Overview Of Hdl Structure and Function In The Systemic Circumentioning

confidence: 99%

“…In addition to cardiovascular disease, there is increasing interest in the connection between HDL and CNS diseases. Despite being separated into two distinct pools by the BBB and the BCSFB, HDL in the periphery and HDL-like particles in the CNS share similar roles in maintaining homeostasis of lipid metabolism and preserving vascular functions [25]. As the major APO in the brain, APOE plays a central role in HDL metabolism and function in the CNS under physiological and pathological conditions ( Figure 1).…”

Section: Overview Of Hdl Structure and Function In The Systemic Circumentioning

confidence: 99%

“…HDL/APOs influence amyloid pathology through a variety of mechanisms, most notably APP trafficking/processing and Aβ production/clearance pathways. APOE is the most extensively investigated HDL-associated APO in modulating amyloid pathology, which has been thoroughly reviewed recently [25,[76][77][78]. In brief, APOE has been reported to participate in all aspects of APP/Aβ metabolism in the brain, including APP processing and Aβ generation, Aβ aggregation, intracellular and extracellular Aβ degradation, and Aβ clearance through the BBB and lymphatic pathways.…”

Section: Amyloid Pathologymentioning

confidence: 99%

“…In the brain, TREM2 is exclusively expressed by microglia. The role of TREM2 in AD has been extensively reviewed [118][119][120][121], in particular the impact of APOE-TREM2 interactions on AD-related neuroinflammation thoroughly covered [25,122]. In brief, as a ligand for TREM2, APOE interacts with TREM2 and drives dysfunctional phenotypes of microglia in aging and in the pathological process of AD.…”

Section: Neuroinflammationmentioning

confidence: 99%

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The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

Chernick

Zhong

2020

Biomolecules

Self Cite

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The role of high-density lipoproteins (HDL) in the cardiovascular system has been extensively studied and the cardioprotective effects of HDL are well established. As HDL particles are formed both in the systemic circulation and in the central nervous system, the role of HDL and its associated apolipoproteins in the brain has attracted much research interest in recent years. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the leading cause of dementia worldwide, for which there currently exists no approved disease modifying treatment. Multiple lines of evidence, including a number of large-scale human clinical studies, have shown a robust connection between HDL levels and AD. Low levels of HDL are associated with increased risk and severity of AD, whereas high levels of HDL are correlated with superior cognitive function. Although the mechanisms underlying the protective effects of HDL in the brain are not fully understood, many of the functions of HDL, including reverse lipid/cholesterol transport, anti-inflammation/immune modulation, anti-oxidation, microvessel endothelial protection, and proteopathy modification, are thought to be critical for its beneficial effects. This review describes the current evidence for the role of HDL in AD and the potential of using small peptides mimicking HDL or its associated apolipoproteins (HDL-mimetic peptides) as therapeutics to treat AD.

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Effect of periodontal treatment on preclinical Alzheimer's disease—Results of a trial emulation approach

Schwahn

Frenzel

Holtfreter

et al. 2021

Alzheimer's & Dementia

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Introduction:We investigated the relationship between periodontal treatment and pre-clinical Alzheimer's disease (AD). Methods:In this quasi-experimental design, 177 periodontally treated patients from the "Greifswald Approach to Individualized Medicine" cohort, which used the same protocols as the population-based Study of Health in Pomerania TREND (SHIP-TREND), and 409 untreated subjects from SHIP-TREND were analyzed. Subjects were younger than 60 years at the magnetic resonance imaging examination, with a median observation period of 7.3 years. Imaging markers for brain atrophy in late-onset AD and brain aging were used as the outcomes.Results: Robust to sensitivity analyses, periodontal treatment had a favorable effect on AD-related brain atrophy (-0.41; 95% confidence interval: -0.70 to -0.12; P = .0051), which corresponds to a shift from the 50th to the 37th percentile of the outcome distribution. For brain aging, the treatment effect was uncertain. Conclusion:Periodontitis is related to pre-clinical AD in our population.

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Peripheral versus central nervous system APOE in Alzheimer’s disease: Interplay across the blood-brain barrier

Cited by 46 publications

References 158 publications

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

Effect of periodontal treatment on preclinical Alzheimer's disease—Results of a trial emulation approach

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