Central Nervous System Lipoproteins

Mahley, Robert W.

doi:10.1161/atvbaha.116.307023

Cited by 334 publications

(161 citation statements)

References 111 publications

(135 reference statements)

Supporting

Mentioning

157

Contrasting

Order By: Relevance

“…Most cholesterol is released by astrocytes in the form of ApoE-containing “high-density lipoprotein (HDL) -like” particles [5]. Complete genetic deficiency of ApoE, or deficiency limited to the CNS, results in a reduction of synapse number that is at least partially due to loss of astrocyte-derived particles [6].…”

Section: Apoe and The Ldl Receptor Familymentioning

confidence: 99%

See 1 more Smart Citation

ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease

Lane-Donovan

Herz

2017

Trends in Endocrinology & Metabolism

120

View full text Add to dashboard Cite

As the population ages, neurodegenerative diseases, such as Alzheimer’s disease (AD), are becoming a significant burden on patients, their families, and health care systems. Neurodegenerative processes may start up to fifteen years before outward signs and symptoms of AD, as evidenced by data from AD patients and mouse models. A major genetic risk factor for late-onset (AD) is the ε4 isoform of apolipoprotein E (ApoE4), which is present in almost 20% of the population. In this review, we discuss the contribution of ApoE receptor signaling to the function of each component of the tripartite synapse - the axon terminal, the post-synaptic dendritic spine, and the astrocyte - and examine how these systems fail in the context of ApoE4 and AD.

show abstract

Section: Apoe and The Ldl Receptor Familymentioning

confidence: 99%

“…Astrocyte-derived ApoE is important for cholesterol transport through ApoE-containing “HDL-like” particles, which play an important role in synaptic development and maintenance [1, 4, 5]. Interestingly, recent data supports the hypothesis that ApoE and the ApoE receptors mediate processes in the astrocyte outside of lipid trafficking.…”

Section: Astrocytesmentioning

confidence: 99%

ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease

Lane-Donovan

Herz

2017

Trends in Endocrinology & Metabolism

120

View full text Add to dashboard Cite

show abstract

“…In the brain, ABAC1 stimulates the lipidation of apoE following its synthesis and secretion from astrocytes [17]. Interestingly, brain and peripheral apoE are produced and regulated independently and are, thus, parts of separate metabolic pools which do not mix [18, 19]. …”

Section: Introductionmentioning

confidence: 99%

“…ApoA-I, though not synthesized in the brain, is present in the central nervous system (CNS), due to its ability to cross the blood brain barrier (BBB) from the periphery [19, 20]. In view of the important role of apoA-I in lipid transport in the periphery, it is presumed that apoA-I plays a similar role in the brain [20–22].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of apoE4 and Activation of ABCA1 on Brain and Plasma Lipoproteins

et al. 2016

View full text Add to dashboard Cite

Apolipoprotein E4 (apoE4), the leading genetic risk factor for Alzheimer's disease (AD), is less lipidated compared to the most common and AD-benign allele, apoE3. We have recently shown that i.p. injections of the ATP-binding cassette A1 (ABCA1) agonist peptide CS-6253 to apoE mice reverse the hypolipidation of apoE4 and the associated brain pathology and behavioral deficits. While in the brain apoE is the main cholesterol transporter, in the periphery apoE and apoA-I both serve as the major cholesterol transporters. We presently investigated the extent to which apoE genotype and CS-6253 treatment to apoE3 and apoE4-targeted replacement mice affects the plasma levels and lipid particle distribution of apoE, and those of plasma and brain apoA-I and apoJ. This revealed that plasma levels of apoE4 were lower and eluted faster following FPLC than plasma apoE3. Treatment with CS-6253 increased the levels of plasma apoE4 and rendered the elution profile of apoE4 similar to that of apoE3. Similarly, the levels of plasma apoA-I were lower in the apoE4 mice compared to apoE3 mice, and this effect was partially reversed by CS-6253. Conversely, the levels of apoA-I in the brain which were higher in the apoE4 mice, were unaffected by CS-6253. The plasma levels of apoJ were higher in apoE4 mice than apoE3 mice and this effect was abolished by CS-6253. Similar but less pronounced effects were obtained in the brain. In conclusion, these results suggest that apoE4 affects the levels of apoA-I and apoJ and that the anti-apoE4 beneficial effects of CS-6253 may be related to both central and peripheral mechanisms.

show abstract

“…APOJ , SORL1 and APOC1 belong to the same lipoprotein metabolism pathway (www.reactome.org) as APOE too. This pathway is critical in redistributing cholesterol and phospholipids in brains, responsible for the apoE4-associated neuropathology including the formation of neurotoxic fragments that have been demonstrated to be involved in the development of AD (Mahley 2016; Jones et al 2010). APOE and APOJ expression in brains is the most abundant among all risk genes for AD.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide significant, replicated and functional risk variants for Alzheimer’s disease

et al. 2017

View full text Add to dashboard Cite

Genome-wide association studies (GWASs) have reported numerous associations between risk variants and Alzheimer’s disease (AD). However, these associations do not necessarily indicate a causal relationship. If the risk variants can be demonstrated to be biologically functional, the possibility of a causal relationship would be increased. In this article, we reviewed all of the published GWASs to extract the genome-wide significant (p<5×10−8) and replicated associations between risk variants and AD or AD-biomarkers. The regulatory effects of these risk variants on the expression of a novel class of non-coding RNAs (piRNAs) and protein-coding RNAs (mRNAs), the alteration of proteins caused by these variants, the associations between AD and these variants in our own sample, the expression of piRNAs, mRNAs and proteins in human brains targeted by these variants, the expression correlations between the risk genes and APOE, the pathways and networks that the risk genes belonged to, and the possible long non-coding RNAs (LncRNAs) that might regulate the risk genes were analyzed, to investigate the potential biological functions of the risk variants and explore the potential mechanisms underlying the SNP-AD associations. We found replicated and significant associations for AD or AD-biomarkers, surprisingly, only at 17 SNPs located in 11 genes/snRNAs/LncRNAs in eight genomic regions. Most of these 17 SNPs enriched some AD-related pathways or networks, and were potentially functional in regulating piRNAs and mRNAs; some SNPs were associated with AD in our sample, and some SNPs altered protein structures. Most of the protein-coding genes regulated by the risk SNPs were expressed in human brain and correlated with APOE expression. We conclude that these variants were most robust risk markers for AD, and their contributions to AD risk was likely to be causal. As expected, APOE and the lipoprotein metabolism pathway possess the highest weight among these contributions.

show abstract

Central Nervous System Lipoproteins

Cited by 334 publications

References 111 publications

ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease

ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease

Differential Effects of apoE4 and Activation of ABCA1 on Brain and Plasma Lipoproteins

Genome-wide significant, replicated and functional risk variants for Alzheimer’s disease

Contact Info

Product

Resources

About