The DOI matches its Crossref record; 100 of the 103 references it cites were found in a registry or an index; 1 of the 95 sources its claims cite were checked for support.
ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease
Open accessAbstract
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 15 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 ɛ4 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 postsynaptic dendritic spine, and the astrocyte - and examine how these systems fail in the context of ApoE4 and AD.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that ApoE receptors (the LDL receptor family) act as central regulators of synaptic function across all three compartments of the tripartite synapse, and that the ApoE4 isoform disrupts these neuromodulatory roles early in Alzheimer's disease. It proposes that ApoE4 drives neuronal dysfunction both by impairing amyloid-beta turnover and by blunting Reelin/ApoE receptor protection of the synapse.
Key findings
- ApoE4 is a major late-onset AD risk factor: one copy roughly triples risk, two copies confer about a 90% lifetime risk, and allele frequency is 15–20%; ApoE2 appears protective and ApoE3 risk-neutral.
- Reelin signaling through Apoer2/Lrp8 and Vldlr phosphorylates Dab1, which boosts NMDAR-mediated calcium influx and LTP while inhibiting GSK3β and tau phosphorylation; Reelin application to hippocampal slices prevents Aβ-induced LTP reduction, and intraventricular Reelin improves learning and memory in mice.
- Aβ oligomers oppose Reelin via calcineurin/STEP-driven NMDAR internalization and via caspase-3/Akt-mediated GSK3β activation, reducing LTP; Reelin-deficient mice overexpressing Aβ are heavily impaired on the Morris Water Maze.
- ApoE4's structural instability (molten globule tendency, aggregation at 37°C) stalls endosomal recycling of ApoE receptors and co-trapped glutamate receptors, producing a state of "Reelin resistance"; ApoE4 targeted-replacement mice and human ApoE4 carriers show reduced dendritic spine complexity.
- Presynaptically, Reelin acting through Apoer2/Vldlr raises intracellular calcium and selectively enhances fusion of VAMP7-containing vesicles; ApoE4 TR mice show decreased glutamate, increased glutamine, and late increases in vglut1.
- Astrocytic Lrp4 mediates agrin-driven ATP release, which is converted to adenosine and suppresses presynaptic glutamate release via A1 receptors; ApoE4 limits astrocytic synaptic pruning and causes the greatest glial activation.
Methods
- Narrative review; no primary data collection or new experiments.
- Synthesizes published human, mouse, and in vitro literature on ApoE, LDL receptor family members, Reelin, and AD pathology.
- Organizes evidence by tripartite synapse compartment (postsynaptic spine, axon terminal, astrocyte) and by signaling pathway (Reelin/Dab1, calcium homeostasis, actin polymerization, endocytic trafficking).
Limitations
- Stated: the authors list unresolved questions, including whether ApoE4 represents gain or loss of function, whether ApoE isoforms affect presynaptic VAMP7-vesicle mobilization, the mechanism by which ApoE influences astrocytic pruning, how Lrp4 increases astrocytic ATP release, and which molecular targets could ameliorate ApoE4's endocytic recycling effects.
- Stated: definitive human evidence that Reelin is protective is largely lacking; the role of Lrp1 in ApoE-isoform effects on pruning "remains to be demonstrated"; the impact of altered presynaptic glutamate production in vivo requires follow-up.
- Evident from the text: as a review it presents no new data, and several mechanistic claims rest on mouse models or slice preparations whose translation to human AD is not established.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
72 Not checked yet · 16 Own interpretation · 3 No basis given · 1 Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“intraventricular injection of Reelin in mice improves learning and memory [30].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Supportedcites [30] Rogers JT 2011 Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density Learn Mem 18 9 558 64 21852430 PMC3166788 source
The Abstract states that purified Reelin was injected bilaterally into the ventricles of wild-type mice and that the mice showed enhanced performance in learning and memory tasks. The Results report faster spatial learning and better memory retention in Reelin-injected mice than in saline-injected mice. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating a role for ApoE in neuronal function prior to amyloid deposition”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“some of these changes are present much earlier in life [16]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
What the sources say
- Not checked yetcites [16] Dean DC 3rd 2014 Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study JAMA Neurol 71 1 11 22 24276092 PMC4056558 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Lrp1 interacts with the N-methyl-D-aspartate receptor (NMDAR), promoting the endocytosis of NMDAR from the cell surface [19].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [19] Maier W 2013 LRP1 is critical for the surface distribution and internalization of the NR2B NMDA receptor subtype Mol Neurodegener 8 25 23866919 PMC3722104 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The primary ligand for these receptors in the CNS is not ApoE, but rather the glycoprotein Reelin [22].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [22] Lee GH D’Arcangelo G 2016 New Insights into Reelin-Mediated Signaling Pathways Front Cell Neurosci 10 122 27242434 PMC4860420 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“ApoE4 hindering Aβ clearance significantly over ApoE3 and ApoE2 [14]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
What the sources say
- Not checked yetcites [14] Castellano JM 2011 Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance Sci Transl Med 3 89 89ra57 PMC3192364 21715678 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the ApoE receptors Apoer2/Lrp8 and Vldlr form a complex with scaffolding proteins, such as PSD-95, and the glutamate receptors [21].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [21] Beffert U 2005 Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2 Neuron 47 4 567 79 16102539 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“A major genetic risk factor for late-onset (AD) is the ε4 isoform of apolipoprotein E (ApoE4)”
- Also stated in: § ApoE, ApoE Receptors, and Alzheimer’s Disease · plain
“Over two decades ago, the ε4 isoform of ApoE (ApoE4) was identified as a major genetic risk factor for late-onset AD (i.e., after 60 years of age) [12].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Abstract
What the sources say
- Not checked yetcites [12] Lutz MW 2016 A Genetics-based Biomarker Risk Algorithm for Predicting Risk of Alzheimer’s Disease Alzheimers Dement (N Y) 2 1 30 44 27047990 PMC4817110 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § ApoE, ApoE Receptors, and Alzheimer’s Disease · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and thus directly increasing amyloid pathology”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“older individuals who are ApoE4 carriers have structural and functional alterations in AD affected areas in the absence of cognitive dysfunction [15]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
What the sources say
- Not checked yetcites [15] Chen Y 2015 Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE varepsilon4 allele Neuropsychopharmacology 40 5 1181 91 25403724 PMC4367462 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 26
- Probably not a substantial claim. 7
In the paper
“Possession of one copy of ApoE4 triples the risk of developing AD, while individuals with two copies have a 90% lifetime risk of developing the disease.”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
What the sources say
- Not checked yetcites [12] Lutz MW 2016 A Genetics-based Biomarker Risk Algorithm for Predicting Risk of Alzheimer’s Disease Alzheimers Dement (N Y) 2 1 30 44 27047990 PMC4817110 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The allele frequency of ApoE4 is 15–20%, with some variation in incidence between populations [13].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
What the sources say
- Not checked yetcites [13] Liu CC 2013 Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy Nat Rev Neurol 9 2 106 18 23296339 PMC3726719 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Conversely, ApoE2 is considered to be protective against AD, while ApoE3 is considered risk-neutral”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE, ApoE Receptors, and Alzheimer’s Disease
What the sources say
- Not checked yetcites [13] Liu CC 2013 Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy Nat Rev Neurol 9 2 106 18 23296339 PMC3726719 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Dab1-mediated activation of Src and Fyn leads to the tyrosine phosphorylation of the NR2 subunits of NMDARs, which causes increased Ca2+ influx when the receptors are activated and also reduces NMDAR endocytosis [27, 28]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“STEP additionally dephosphorylates and deactivates Fyn, enhancing the overall effect of STEP on NMDAR endocytosis [36].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [36] Nguyen TH 2002 Striatal enriched phosphatase 61 dephosphorylates Fyn at phosphotyrosine 420 J Biol Chem 277 27 24274 9 11983687 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the ApoE receptors activated by Reelin are essential in maintaining the signal strength over the noise of rising Ca2+ levels induced by AD-promoting mechanisms. This mechanism affords protection to the synapse by maintaining synaptic strength during the early stages of AD until Aβ and τ accumulate to such levels that the system breaks down and synaptic loss ensues.”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Calcium Dysregulation and ApoE receptors
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Dab1 activates phosphoinositol-3 (PI3) kinase and subsequently Akt, which phosphorylates glycogen synthase kinase 3β (GSK3β) at its inhibitory Ser-9 phosphorylation site. This reduces the phosphorylation of numerous targets of GSK3β, the most relevant of which in the context of AD is the microtubule-associated protein τ [25].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [25] Herz J Chen Y 2006 Reelin, lipoprotein receptors and synaptic plasticity Nat Rev Neurosci 7 11 850 9 17053810 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“GSK3β activation reduces synaptic long-term potentiation (LTP) and provides a potential biochemical mechanism by which Aβ can induce τ hyperphosphorylation [39].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [39] Zhu LQ 2007 Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments J Neurosci 27 45 12211 20 17989287 PMC6673262 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The main effect of higher resting levels of Ca2+ appears to be to tip the balance of synaptic plasticity towards LTD. The net result of this would be memory trace erasure and loss of synapses.”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Calcium Dysregulation and ApoE receptors
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Aβ oligomers reduce activity of LIMK, which in turns leads to dephosphorylated, active cofilin, depolymerization of actin filaments and the generation of actin rods [66].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Post-synaptic actin polymerization
What the sources say
- Not checked yetcites [66] Zhao L 2006 Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease Nat Neurosci 9 2 234 42 16415866 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“actin polymerization and dendritic spine growth exhibit a net increase in the presence of Reelin, and mice that overexpress Reelin have higher spine density and increased spine complexity [64, 65].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Post-synaptic actin polymerization
What the sources say
- Not checked yetcites [64] Chai X 2009 Reelin stabilizes the actin cytoskeleton of neuronal processes by inducing n-cofilin phosphorylation at serine3 J Neurosci 29 1 288 99 19129405 PMC6664910 source
- Not checked yetcites [65] Bosch C 2016 Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells Cereb Cortex PMC5066826 27624722 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“ApoE has two structural domains, an N-terminal domain, which is responsible for interaction with ApoE receptors, and a C-terminal domain, which is responsible for lipoprotein binding [68].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE and Endocytic Trafficking
What the sources say
- Not checked yetcites [68] Zhong N Weisgraber KH 2009 Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure J Biol Chem 284 10 6027 31 18948255 PMC2649104 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“when ApoE4 is present, the final recycling step is delayed and the process is stalled in the endosome, presumably due to the propensity of ApoE4 to form molten globules at the lower pH of the endosome [69, 71].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE and Endocytic Trafficking
What the sources say
- Not checked yetcites [69] Morrow JA 2002 Apolipoprotein E4 forms a molten globule. A potential basis for its association with disease J Biol Chem 277 52 50380 5 12393895 source
- Not checked yetcites [71] Heeren J 2004 Impaired recycling of apolipoprotein E4 is associated with intracellular cholesterol accumulation J Biol Chem 279 53 55483 92 15485881 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The presence of an arginine at position 112 promotes the formation of a salt bridge between Arg-61 and Glu-255, leading to a “domain interaction” between the N- and C-terminals. As a result, ApoE4 has a greater tendency to form molten globules over the other ApoE isoforms, as well as a greater propensity to aggregate at 37°C [69, 70].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE and Endocytic Trafficking
What the sources say
- Not checked yetcites [69] Morrow JA 2002 Apolipoprotein E4 forms a molten globule. A potential basis for its association with disease J Biol Chem 277 52 50380 5 12393895 source
- Not checked yetcites [70] Hatters DM 2006 Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils J Mol Biol 361 5 932 44 16890957 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ApoE binds the receptors at a different site from Reelin, and thus does not directly affect receptor signaling by hindering Reelin engagement; however, the ApoE isoforms do affect receptor trafficking.”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE and Endocytic Trafficking
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“suggesting a reduced ability of presynaptic ApoE4 neurons to convert glutamine to glutamate and a compensatory increase in vesicular glutamate loading [75].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Presynaptic Roles of ApoE Receptors
What the sources say
- Not checked yetcites [75] Dumanis SB 2013 APOE genotype affects the pre-synaptic compartment of glutamatergic nerve terminals J Neurochem 124 1 4 14 22862561 PMC3509249 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ApoE4 targeted replacement mice have a reduction in dendritic spine complexity, a finding that is mirrored in human ApoE4 carriers [67].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Post-synaptic actin polymerization
What the sources say
- Not checked yetcites [67] Ji Y 2003 Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer’s disease patients Neuroscience 122 2 305 15 14614898 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“With age, Reelin levels are reduced in the brain and in AD, Reelin levels are particularly reduced in the entorhinal cortex [44].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [44] Chin J 2007 Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer’s disease J Neurosci 27 11 2727 33 17360894 PMC6672562 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [1] Lane-Donovan C 2014 More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration Neuron 83 4 771 87 25144875 PMC4240629 source
- Not checked yetcites [4] Pfrieger FW 2010 Role of glial cells in the formation and maintenance of synapses Brain Res Rev 63 1–2 39 46 19931561 source
- Not checked yetcites [5] Mahley RW 2016 Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism Arterioscler Thromb Vasc Biol 36 7 1305 15 27174096 PMC4942259 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Reelin signaling activates PI3kinase, as described above [61]. In turn, PI3kinase initiates a signaling pathway that induces phosphorylation of LIM kinase-1 (LIMK-1), which in turn phosphorylates cofilin at an inhibitory site, blocking the actin-depolymerizing activity of cofilin [62, 63].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Post-synaptic actin polymerization
What the sources say
- Not checked yetcites [61] Bock HH 2003 Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination J Biol Chem 278 40 38772 9 12882964 source
- Not checked yetcites [62] Caroni P 2014 Synapse rearrangements upon learning: from divergent-sparse connectivity to dedicated sub-circuits Trends Neurosci 37 10 604 14 25257207 source
- Not checked yetcites [63] Mizuno K 2013 Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation Cell Signal 25 2 457 69 23153585 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aβ binds to α7 nicotinic acetylcholine receptors (α7 nAChRs) and to metabotropic glutamate receptors, in particular mGluR5 [31–33].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Reelin, ApoE receptors, and Glutamate Signaling
What the sources say
- Not checked yetcites [31] Dineley KT 2001 Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer’s disease J Neurosci 21 12 4125 33 11404397 PMC6762764 source
- Not checked yetcites [32] Renner M 2010 Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5 Neuron 66 5 739 54 20547131 PMC3111138 source
- Not checked yetcites [33] Lauren J 2009 Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers Nature 457 7233 1128 32 19242475 PMC2748841 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
In the paper
“ApoE exists in the human population in three isoforms, which differ at only two residues, 112 and 158. ApoE2 has a cysteine at both positions, ApoE3 has a cysteine at position 112 and an arginine at position 158, and ApoE4 has arginines at both positions [68].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE and Endocytic Trafficking
What the sources say
- Not checked yetcites [68] Zhong N Weisgraber KH 2009 Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure J Biol Chem 284 10 6027 31 18948255 PMC2649104 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this way, ApoE4 induces a state of “Reelin resistance” that likely affects more than synaptic plasticity (e.g., Ca2+ homeostasis, spine remodeling, and the pre-synaptic and astrocytic roles described below).”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > ApoE and Endocytic Trafficking
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“for its role in neuromuscular junction (NMJ) development and in the maintenance of the adult NMJ”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [87] Selcen D 2015 Impaired Synaptic Development, Maintenance, and Neuromuscular Transmission in LRP4-Related Myasthenia JAMA Neurol 72 8 889 96 26052878 PMC4532561 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“glial activation is an indication of pro-inflammatory changes that is commonly found in AD brains”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [98] Heppner FL 2015 Immune attack: the role of inflammation in Alzheimer disease Nat Rev Neurosci 16 6 358 72 25991443 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the role of anti-Lrp4 and anti-MuSK antibodies in myasthenia gravis [87]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [87] Selcen D 2015 Impaired Synaptic Development, Maintenance, and Neuromuscular Transmission in LRP4-Related Myasthenia JAMA Neurol 72 8 889 96 26052878 PMC4532561 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“at the NMJ, Lrp4, APP and muscle-specific kinase (MuSK) form a complex to prepattern the muscle [88–90]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [88] Choi HY 2013 APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice Elife 2 e00220 23986861 PMC3748711 source
- Not checked yetcites [89] Kim N 2008 Lrp4 is a receptor for Agrin and forms a complex with MuSK Cell 135 2 334 42 18848351 PMC2933840 source
- Not checked yetcites [90] Zhang B 2008 LRP4 serves as a coreceptor of agrin Neuron 60 2 285 97 18957220 PMC2743173 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Lrp1 is highly expressed in astrocytes, where it is responsible for phagocytosis of degraded myelin [78, 79].”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [78] Cahoy JD 2008 A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function J Neurosci 28 1 264 78 18171944 PMC6671143 source
- Not checked yetcites [79] Gaultier A 2009 Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis J Cell Sci 122 Pt 8 1155 62 19299462 PMC2714439 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Lrp4 is more commonly known as the gene defective in Cenani-Lenz syndrome [83–86]”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [83] Karner CM 2010 Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation--a mouse model for Cenani-Lenz syndrome PLoS One 5 4 e10418 20454682 PMC2861670 source
- Not checked yetcites [84] Johnson EB 2005 Abnormal development of the apical ectodermal ridge and polysyndactyly in Megf7-deficient mice Hum Mol Genet 14 22 3523 38 16207730 source
- Not checked yetcites [85] Johnson EB 2006 Defective splicing of Megf7/Lrp4, a regulator of distal limb development, in autosomal recessive mulefoot disease Genomics 88 5 600 9 16963222 source
- Not checked yetcites [86] Li Y 2010 LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome Am J Hum Genet 86 5 696 706 20381006 PMC2869043 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“by two distinct mechanisms: impairing the turnover of Aβ, thereby accelerating amyloid deposition”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Concluding Remarks and future perspectives
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Mechanisms of ApoE and Lrp4 function observed in mouse models apply to human Alzheimer's disease.
None of the sources cited for this claim have been checked yet.
In the paper
“Agrin is released from the motor neuron and signals through APP, MuSK and Lrp4 to recruit nicotinic acetylcholine receptors (AChRs).”
§ ApoE, ApoE receptors, and the Synapse in Alzheimer’s Disease > Astrocytes
What the sources say
- Not checked yetcites [88] Choi HY 2013 APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice Elife 2 e00220 23986861 PMC3748711 source
- Not checked yetcites [89] Kim N 2008 Lrp4 is a receptor for Agrin and forms a complex with MuSK Cell 135 2 334 42 18848351 PMC2933840 source
- Not checked yetcites [90] Zhang B 2008 LRP4 serves as a coreceptor of agrin Neuron 60 2 285 97 18957220 PMC2743173 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Mechanisms of ApoE/ApoE receptor signaling and ApoE4 effects observed in mouse models and cell studies are relevant to human Alzheimer's disease.
“ApoE4 targeted replacement mice have a reduction in dendritic spine complexity, a finding that is mirrored in human ApoE4 carriers [67].”
The paper relies on this without support.
The tripartite synapse framework captures the relevant sites of ApoE/ApoE receptor action in Alzheimer's disease.
“We divide our discussion based on the three components of the tripartite synapse – the post-synaptic spine, the axon terminal, and the astrocyte – and delineate the newly discovered roles of ApoE receptor signaling at each of these compartments (Figure 1).”
The paper relies on this without support.
Mechanisms of ApoE and Lrp4 function observed in mouse models apply to human Alzheimer's disease.
“ApoE4 promotes neuronal dysfunction at the earliest stages of the pathology, leading up to the clinical manifestation of AD”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Of these, ApoE receptor-2 (Apoer2, a.k.a. LRP8) is the best characterized. It is present both pre- as well as postsynaptically where it primarily functions as a receptor for Reelin (Bal et al., 2013; Beffert et al., 2005; Lane-Donovan and Herz, 2017).”
From Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer’s disease (2018) · cites this paper as Lane-Donovan and Herz, 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“these data add nevertheless further support to our model which postulates impaired neuronal endosomal vesicle trafficking as the root cause for the increased AD risk imposed by ApoE4 (Chen et al., 2005; Chen et al., 2010; Lane-Donovan and Herz, 2017; Lane-Donovan et al., 2014).”
From Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer’s disease (2018) · cites this paper as Lane-Donovan and Herz, 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The binding of RELN results in the clustering and activation of VLDLr and APOEr2, initiating a signaling pathway that leads to the activation of Dab1 (refs. 4,7–9).”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“APOE binds to cell surface receptors, such as low‐density lipoprotein receptor (LDLR), LDLR‐related protein 1 (LRP1), very low‐density lipoprotein receptor (VLDLR), and apolipoprotein E receptor 2 (APOER2 or LRP8). 2 , 14 , 15”
From Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [14]
Citations
Cites
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BackgroundGenome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · cited 1×
“This is partially due to the fact that ApoE expression, in both mice and humans, begins relatively late in development [46, 47].”
Background2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
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“Jo J, et al. Abeta(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3beta.”
BackgroundInfluentialApolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · cited 2×
“The allele frequency of ApoE4 is 15–20%, with some variation in incidence between populations [13].”
BackgroundCahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · cited 1×
“Lrp1 is highly expressed in astrocytes, where it is responsible for phagocytosis of degraded myelin [78, 79].”
BackgroundImmune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 8×
“PP2B regulates levels and activity of striatal-enriched protein tyrosine phosphatase (STEP) [34].”
InfluentialCellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009) · Nature · doi:10.1038/nature07761 · Cited by 1,560
Cited by
Sorted by citations
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722
Microglia-Mediated Synapse Loss in Alzheimer's Disease
Rajendran, L., & Paolicelli, R. C. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.1136-17.2017 · Cited by 355
“ApoE is a major regulator of lipid homeostasis present in three allelic variants 2, 3, or 4; and although its function is varied (for review, see Lane-Donovan and Herz, 2017), it primarily transports cholesterol to neurons via specific ApoE receptors.”
BackgroundBeyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348
The integration of inflammaging in age-related diseases
Fülöp, T., Witkowski, J. M., Olivieri, F., & Larbi, A. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.003 · Cited by 368
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306
Challenges and hopes for Alzheimer’s disease
Tatulian, S. A. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.016 · Cited by 291
Apolipoprotein E in lipid metabolism and neurodegenerative disease
Yang, L. G., March, Z. M., Stephenson, R. A., & Narayan, P. S. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.05.002 · Cited by 286
“The best understoodmechanism of transport is via the low-density lipoprotein receptor (LDLR) [14], and novel APOE receptors are emerging [15,16].”
Rab GTPases and Membrane Trafficking in Neurodegeneration
Kiral, F. R., Kohrs, F. E., Jin, E. J., & Hiesinger, P. R. (2018) · Current Biology · doi:10.1016/j.cub.2018.02.010 · Cited by 249
Kemp, S. B., Carpenter, E. S., Steele, N. G., Donahue, K. L., Nwosu, Z. C., Pacheco, A., Velez-Delgado, A., Menjivar, R. E., Lima, F., The, S., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3929 · Cited by 197
“…our scRNA-seq data that KPC tumor cells express 4 of the major ApoE receptors: low-density lipoprotein receptor (LDLR), very low-density lipoprotein receptor (VLDLR), low-density lipoprotein receptor related protein 1 (LRP1), and low-density lipoprotein receptor-related protein 8 (LRP8) (34) (Fig.”
BackgroundInfluentialNoncoding RNAs in Alzheimer's disease
Idda, M. L., Munk, R. B., Abdelmohsen, K., & Gorospe, M. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1463 · Cited by 211
“Apolipoprotein E (APOE) is a lipid carrier present in the peripheral and central nervous systems (CNS) that supports membrane homeostasis and injury repair in the brain (Lane-Donovan & Herz, 2017; Mahley, 2016; Zhao, Liu, Qiao, & Bu, 2017).”
BackgroundAPOE4 derived from astrocytes leads to blood–brain barrier impairment
Jackson, R. J., Meltzer, J. C., Nguyen, H., Commins, C., Bennett, R. E., Hudry, E., & Hyman, B. T. (2022) · Brain · doi:10.1093/brain/awab478 · Cited by 205
Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man
Lopera, F., Marino, C., Chandrahas, A. S., O’Hare, M., Villalba-Moreno, N. D., Aguillon, D., Baena, A., Sanchez, J. S., Vila-Castelar, C., Ramirez Gomez, L., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02318-3 · Cited by 192
Updates in Alzheimer's disease: from basic research to diagnosis and therapies
Liu, E., Zhang, Y., & Wang, J. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00432-x · Cited by 241
“VLDL-R and LDL-R are predominantly located on the astrocyte membrane, while LRP is mainly distributed in neurons and activated astrocytes [45].”
BackgroundPark, J., Jang, S., Lee, D., Lee, J.-H., Kang, U., Chang, H., Kim, H. J., Han, S.-H., Seo, J., Choi, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20440-5 · Cited by 227
Moulton, M. J., Barish, S., Ralhan, I., Chang, J., Goodman, L. D., Harland, J. G., Marcogliese, P. C., Johansson, J. O., Ioannou, M. S., & Bellen, H. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2112095118 · Cited by 180
Role of the peripheral innate immune system in the development of Alzheimer's disease
Page, A. Y. L., Dupuis, G., Frost, E. H., Larbi, A., Pawelec, G., Witkowski, J. M., & Fülöp, T. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.019 · Cited by 162
“The proinflammatory effect of these microbial products may be enhanced by the well-known ApoE4 genotype (Lane-Donovan and Herz, 2017) as it was shown in mice (Vitek et al.”
Beyond the CNS: The many peripheral roles of APOE
Martínez-Martínez, A. B., Torres-Perez, E., Devanney, N., Del Moral, R., Johnson, L. A., & Arbones-Mainar, J. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104809 · Cited by 149
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Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease
Wadhwani, A. R., Affaneh, A., Van Gulden, S., & Kessler, J. A. (2019) · Annals of Neurology · doi:10.1002/ana.25455 · Cited by 142
“Effects of APOE isoform on calcium homeostasis have heretofore been attributed to differential binding of glial APOE on neuronal APOE receptors.(53) Our observations indicate that endogenous expression of E4 in neurons sensitizes them to calcium dysregulation, independently of glial APOE.”
BackgroundThe Epigenetics of Alzheimer’s Disease: Factors and Therapeutic Implications
Liu, X., Jiao, B., & Shen, L. H. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00579 · Cited by 153
“Among them, the ε4 isoform of apolipoprotein E (ApoE4) is well-known as the strongest genetic risk factor for LOAD (Lane-Donovan and Herz, 2017).”
BackgroundInfluentialMillan, M. J. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.03.004 · Cited by 151
Machine learning and digital biomarkers can detect early stages of neurodegenerative diseases
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“Processes correlated with AD begin over 30 years, whereas cognitive changes begin over about 15–11 years, before the first AD symptoms [6,7].”
BackgroundRobert, J., Button, E. B., Yuen, B., Gilmour, M., Kang, K., Bahrabadi, A., Stukas, S. K., Zhao, W., Kulić, I., & Wellington, C. L. (2017) · eLife · doi:10.7554/elife.29595 · Cited by 118
“ApoE isoforms differentially reduce amyloid accumulation in bipartite vessels Genetic variation in APOE represents the most common genetic risk factor for AD, with APOE4 being detrimental and APOE2 protective (Zlokovic, 2013).”
Neuroinflammation in Alzheimer’s disease: insights from peripheral immune cells
Zhang, Q., Yang, G., Luo, Y., Jiang, L., Chi, H., & Tian, G. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00445-0 · Cited by 138
New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease
Zhang, F., Zhong, R.-J., Cheng, C., Li, S., & Le, W.-D. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00565-5 · Cited by 105
The cell biology of APOE in the brain
Windham, I. A., & Cohen, S. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.09.004 · Cited by 103
Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer’s disease
Xian, X., Pohlkamp, T., Durakoglugil, M. S., Wong, C. H., Beck, J. K., Lane-Donovan, C., Plattner, F., & Herz, J. (2018) · eLife · doi:10.7554/elife.40048 · Cited by 98
“It is present both pre- as well as postsynaptically where it primarily functions as a receptor for Reelin (Bal et al., 2013; Beffert et al., 2005; Lane-Donovan and Herz, 2017).”
BackgroundResultInfluentialSelf-citationThe ApoE receptors Vldlr and Apoer2 in central nervous system function and disease
Lane-Donovan, C., & Herz, J. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075507 · Cited by 94
Self-citationRoles of ApoE4 on the Pathogenesis in Alzheimer’s Disease and the Potential Therapeutic Approaches
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Consequences of Metabolic Disruption in Alzheimer's Disease Pathology
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The Ubiquitin System in Alzheimer’s Disease
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Astrocyte-secreted glypican-4 drives APOE4-dependent tau hyperphosphorylation
Saroja, S. R., Gorbachev, K., Julia, T., Goate, A. M., & Pereira, A. C. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2108870119 · Cited by 75
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From degenerative disease to malignant tumors: Insight to the function of ApoE
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Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics
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The Potential Role of Ferroptosis in Alzheimer’s Disease
Zhang, G., Zhang, Y.-R., Shen, Y., Wang, Y., Zhao, M. L., & Sun, L. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201369 · Cited by 71
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A role of low-density lipoprotein receptor-related protein 4 (LRP4) in astrocytic Aβ clearance
Zhang, H., Chen, W., Tan, Z., Zhang, L., Dong, Z., Cui, W., Zhao, K., Wang, H., Jing, H., Cao, R., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0250-20.2020 · Cited by 58
“Third, Ab clearance is regulated by LDLR family members in particular LDLR and LRP1 (LDLR-related protein 1) (LaneDonovan et al., 2014; Lane-Donovan and Herz, 2017).”
BackgroundHishimoto, A., Pletnikova, O., Lang, D. L., Troncoso, J. C., Egan, J. M., & Liu, Q.-R. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0475-2 · Cited by 62
Pericytes Across the Lifetime in the Central Nervous System
Bennett, H. C., & Kim, Y. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.627291 · Cited by 49
Apolipoprotein E and Atherosclerosis
Marais, A. D. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00933-4 · Cited by 53
The translational potential of cholesterol-based therapies for neurological disease
Valenza, M., Birolini, G., & Cattaneo, E. F. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00864-5 · Cited by 48
László, Z. I., & Lele, Z. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.972059 · Cited by 49
“In addition, APOE4 also influences vesicular turnover and receptor recycling leading to altered Reelin and glutamate signaling (Lane-Donovan and Herz, 2017).”
BackgroundXun, C., Ge, L., Tang, F. R., Wang, L., Zhuo, Y., Long, L., Qi, J., Hu, L., Duan, D., Chen, P., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110584 · Cited by 47
NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load
Pohlkamp, T., Xian, X., Wong, C. H., Durakoglugil, M. S., Werthmann, G. C., Saido, T. C., Evers, B. M., White, C. L., Connor, J., Hammer, R. E., et al. (2021) · eLife · doi:10.7554/elife.72034 · Cited by 46
“We previously showed that ApoE4, in contrast to ApoE3 and ApoE2, prevents Reelin- mediated glutamate receptor insertion at the synapse, a state we refer to as ApoE4- mediated Reelin resistance (Chen et al., 2010; Durakoglugil et al., 2009; Lane- Donovan and Herz, 2017; Lane- Donovan et al., 2014; Xian et al., 2018).”
BackgroundInfluentialSelf-citationHan, J. S., Lu, C., Meng, Q., Halim, A., Yean, T. J., & Wu, G. (2019) · Nutrition & Metabolism · doi:10.1186/s12986-019-0409-9 · Cited by 38
A multi‐hit hypothesis for an APOE4 ‐dependent pathophysiological state
Steele, O. G., Stuart, A. C., Minkley, L., Shaw, K., Bonnar, O., Anderle, S., Penn, A. C., Rusted, J., Serpell, L., Hall, C., et al. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15685 · Cited by 44
“Homeostatic control of cellular calcium levels is crucial for regulating neuronal activity and a myriad of processes including cell signalling cascades, organelle function and gene expression (Foster, 2007; Lane-Donovan et al., 2014; Lane-Donovan & Herz, 2017).”
BackgroundLong Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease
Lan, Z., Chen, Y., Jin, J., Xu, Y., & Zhu, X. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.821002 · Cited by 45
Neuronal ApoE4 in Alzheimer’s disease and potential therapeutic targets
Zhang, L., Xia, Y., & Gui, Y. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1199434 · Cited by 41
“Kounnas et al. demonstrated that LRP 1 binds to Kunitzcontaining eggs outside the cyto-soluble APP of the leukocyte inhibitor (KPI) domain (APP 751 and APP 770) and mediates their cellular catabolism (Kounnas et al., 1995; Trommsdorff et al., 1998; Pietrzik et al., 2004).”
BackgroundInfluentialWelcome, M. O. (2020) · PharmaNutrition · doi:10.1016/j.phanu.2020.100176 · Cited by 41
Revolution of Resting-State Functional Neuroimaging Genetics in Alzheimer’s Disease
Chiesa, P. A., Cavedo, E., Lista, S., Thompson, P. M., & Hampel, H. J. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.06.002 · Cited by 35
“Regulates amyloid-b (Ab) oligomerization, aggregation, and receptor-mediated clearance, brain lipid transport, glucose metabolism, neuronal signaling, and neuroinflammation [26,82,83].”
BackgroundLilrB3 is a putative cell surface receptor of APOE4
Zhou, J., Wang, Y., Huang, G., Yang, M., Zhu, Y., Jin, C., Jing, D., Ji, K., & Shi, Y. (2023) · Cell Research · doi:10.1038/s41422-022-00759-y · Cited by 44
“This is also true for a number of other cell surface receptors.(1,62,86,87) In contrast to TREM2, the LilrB/PirB family receptors contain the ITIMs on the intracellular side, binding of two APOE4 molecules to two LilrB3 receptors effectively brings their respective ITIMs to close proximity.”
BackgroundEmerging Role of microRNAs in Dementia
Ramakrishna, S., & Muddashetty, R. S. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.046 · Cited by 40
Evolving therapeutic interventions for the management and treatment of Alzheimer’s disease
Ahmad, F., Karan, A., Sharma, R., Sharma, N. S., Sundar, V., Jayaraj, R. L., Mukherjee, S., & DeCoster, M. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102229 · Cited by 40
SynBot is an open-source image analysis software for automated quantification of synapses
Savage, J. T., Ramirez, J. J., Risher, W. C., Wang, Y., Irala, D., & Eroğlu, Ç. (2024) · Cell Reports Methods · doi:10.1016/j.crmeth.2024.100861 · Cited by 53
“10 Therefore, studying synapse connectivity is crucial to understanding how neuronal circuits are established during development, remodeled throughout life, and impacted by diseases.”
Ramakrishna, S., Jhaveri, V., Konings, S. C., Nawalpuri, B., Chakraborty, S., Holst, B., Schmid, B., Gouras, G. K., Freude, K., & Muddashetty, R. S. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0435-21.2021 · Cited by 34
Surala, M., Soso-Zdravkovic, L., Munro, D. A. D., Rifat, A., Ouk, K., Vida, I., Priller, J., & Madry, C. (2024) · EMBO Reports · doi:10.1038/s44319-024-00130-9 · Cited by 37
“While IL-10 plays a role in synapse formation (Lim et al, 2013), ApoE controls the rate of synaptic pruning by astrocytes (Chung et al, 2016) and can affect glutamatergic transmission in multiple ways via signaling through synaptic ApoE receptors (Lane-Donovan and Herz, 2017).”
BackgroundThe role of UNC5C in Alzheimer’s disease
Li, Q., Wang, B.-L., Sun, F.-R., Li, J., Cao, X., & Tan, L. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.43 · Cited by 29
Mata‐Balaguer, T., Cuchillo‐Ibáñez, I., Calero, M., Ferrer, I., & Sáez‐Valero, J. (2018) · The FASEB Journal · doi:10.1096/fj.201700736rr · Cited by 28
“The possibility that reelin dysfunction and the alteration of ApoER2 processing ultimately influences synaptic function (67, 68) points to a role for these proteins in AD progression.”
BackgroundOpposing Roles of apolipoprotein E in aging and neurodegeneration
Hudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900325 · Cited by 30
“…between A β and speci fi c cellular receptors (such as APP itself, as recently reported [Wang et al, 2017], TREM2 [Yeh et al, 2016], or any other APOE receptors [Holtzman et al, 2012; Lane-Donovan & Herz, 2017]) to initiate various deleterious molecular cascades in neurons or even in glial cells.”
BackgroundJiang, S., Li, X., Li, Y., Chang, Z., Yuan, M., Zhang, Y., Zhu, H., Xiu, Y., Cong, H., Yin, L., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adg5116 · Cited by 30
“In particular, APOE, one of the abundant apolipoprotein released by astrocytes in the brain ( 37 ), is further enriched in ADEVs isolated from AQP4-Ab–seropositive patients with NMOSD.”
BackgroundMolecular recognition of the interaction between ApoE and the TREM2 protein
Mai, Z., Wei, W., Yu, H., Chen, Y., Wang, Y., & Ding, Y. (2022) · Translational Neuroscience · doi:10.1515/tnsci-2022-0218 · Cited by 32
Therapeutic potential of ApoE-mimetic peptides in CNS disorders: Current perspective
Ahmed, S., Pande, A. H., & Sharma, S. S. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114051 · Cited by 29
Mhatre‐Winters, I., Eid, A., Han, Y., Tieu, K., & Richardson, J. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179829 · Cited by 26
Günaydin, C., Sondhi, D., Kaminsky, S. M., Lephart, H. C., Leopold, P. L., Hackett, N. R., Khanna, R., & Crystal, R. G. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.11.003 · Cited by 26
Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development
DePew, A. T., & Mosca, T. J. (2021) · Journal of Developmental Biology · doi:10.3390/jdb9010009 · Cited by 24
Plasma Apolipoprotein E Monomer and Dimer Profile and Relevance to Alzheimer’s Disease
Patra, K., Giannisis, A., Edlund, A. K., Sando, S. B., Lauridsen, C., Berge, G., Grøntvedt, G. R., Bråthen, G., White, L. R., & Nielsen, H. M. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-190175 · Cited by 22
Apolipoprotein E Recognizes Alzheimer's Disease Associated 3‐O Sulfation of Heparan Sulfate
Mah, D., Zhu, Y., Su, G., Zhao, J., Canning, A., Gibson, J. M., Song, X., Stancanelli, E., Xu, Y., Zhang, F., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202212636 · Cited by 26
Molecular subtyping of Alzheimer’s disease with consensus non-negative matrix factorization
Zheng, C., & Xu, R. (2021) · PLoS ONE · doi:10.1371/journal.pone.0250278 · Cited by 21
Ramsden, C. E., Keyes, G. S., Calzada, E., Horowitz, M. S., Zamora, D., Jahanipour, J., Sedlock, A., Indig, F. E., Moaddel, R., Kapogiannis, D., et al. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-220071 · Cited by 19
Zarini-Gakiye, E., Amini, J., Sanadgol, N., Vaezi, G., & Kazem, P. (2020) · Current Molecular Pharmacology · doi:10.2174/1874467213666200422090135 · Cited by 22
Evaluation of the Common Molecular Basis in Alzheimer’s and Parkinson’s Diseases
Rana, P., Franco, E. F., Rao, Y., Syed, K., Barh, D., Azevedo, V., Ramos, R. T. J., & Ghosh, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153730 · Cited by 22
Moos, P. J., Cheminant, J. R., Cowman, S. J., Noll, J., Wang, Q.-M., Musci, T. S., & Venosa, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1425466 · Cited by 19
The Role of MAPK's Signaling in Mediating ApoE4-Driven Pathology In Vivo
Salomon‐Zimri, S., Koren-Iton, A., Angel, A., Ben‐Zur, T., Offen, D., & Michaelson, D. M. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190228120254 · Cited by 17
Neuroglial Advances: New Roles for Established Players
Verkhratsky, A., Li, B., Niu, J., Lin, S.-S., Su, Y., Jin, W., Li, Y., Jiang, S., Yi, C., Shi, F., et al. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70080 · Cited by 19
“We found (through proteomic screening) a remarkable increase in apo-lipoprotein E (APOE, the lipoprotein released by astrocytes in the brain (Lane-Donovan and Herz 2017)) rich ADEVs in patients with AQP4- Abs-positive NMOSD as well as in a murine model of NMOSD (Figure 5).”
Hu, H., Wan, S., Hu, Y., Wang, Q., Li, H., & Zhang, N. (2025) · Annals of Medicine · doi:10.1080/07853890.2024.2445194 · Cited by 20
“Extensive experimental data suggest that APOE is primarily secreted by astrocytes in the brain [138,139] and serves as the main lipid carrier within the CNS [140].”
Aquino, R., de Concini, V., Dhénain, M., Lam, S., Gosset, D., Baquedano, L., Forero, M. G., Menuet, A., Baril, P., & Pichon, C. (2023) · Cells · doi:10.3390/cells12050694 · Cited by 21
Liu, S., Yang, S., Zhu, X., Li, X., Zhang, X., Zhou, X., Cheng, H., Huo, F.-Q., Mao, Q., & Liang, L. (2023) · Biology Direct · doi:10.1186/s13062-023-00444-z · Cited by 16
“APOE is primarily expressed in astrocytes in both the brain and the spinal cord, as well as in the glia surrounding the sensory neurons in DRGs, and the non-myelinating Schwann cells of peripheral nerves [9, 17, 26].”
BackgroundInfluentialApoE4 attenuates cortical neuronal activity in young behaving apoE4 rats
Har-Paz, I., Arieli, E., & Moran, A. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105373 · Cited by 14
“The prevalence of the E4 allele of the apolipoprotein E (apoE4) gene in late-onset Alzheimer’s disease (AD) patients is well established (Huang, 2011; Lane-Donovan and Herz, 2017).”
Zhu, P., Xiao, L., & Wang, Y. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-025-00721-1 · Cited by 19
Gene therapy: an alternative to treat Alzheimer’s disease
Doshi, V., Joshi, G., Sharma, S., & Choudhary, D. K. (2023) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-023-02873-z · Cited by 14
Gao, H., Zheng, W., Li, C., & Xu, H. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111582 · Cited by 14
Durakoglugil, M. S., Wasser, C. R., Wong, C. H. Y., Pohlkamp, T., Xian, X., Lane‐Donovan, C., Fritschle, K., Nästle, L., & Herz, J. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0388-21.2021 · Cited by 14
“Considering the spectrum of neuromodulatory roles of Reelin (Wasser and Herz, 2016; Lane-Donovan and Herz, 2017), our findings suggest that Reelin is regulating pathways that are critical for mGluR-mediated LTD. Reelin cKOmice have elevated STEP61 levels LTD induction depends on both the…”
BackgroundSelf-citationKuang, L., Jia, J., Zhao, D., Xiong, F., Han, X., Wang, Y., & Initiative, A. D. N. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00188 · Cited by 13
“…al., 2009; Lambert et al., 2013; Yu et al., 2019) for the pathogenesis (Karch and Goate, 2015) of AD indicate the apolipoprotein E (APOE) e4 allele (Lane-Donovan and Herz, 2017) involves the accumulation of Amyloid-β (Caselli et al., 2010), leading to increasing Frontiers in Aging Neuroscience |…”
BackgroundHuang, Y. A., Zhou, B., Nabet, A. M., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/460899 · Cited by 14
SynBot: An open-source image analysis software for automated quantification of synapsesPreprint
Savage, J. T., Ramirez, J., Risher, W. C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.26.546578 · Cited by 13
Han, L., Yang, Y., Hou, C., Huang, Y., Zhou, L., Zheng, J., Lv, G., Mao, R., Chen, S., Xu, P., et al. (2021) · Bioscience Reports · doi:10.1042/bsr20210391 · Cited by 13
“Mutations or dysregulation of SAPs in the central nervous system causes synapse dysfunction, thereby promoting the progression of various neurodegenerative diseases (6-11).”
BackgroundMoulton, M. J., Barish, S., Ralhan, I., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.03.433580 · Cited by 13
An Update on the Role of Common Genetic Variation Underlying Substance Use Disorders
Johnson, E. C., Chang, Y., & Arpana Agrawal, A. (2020) · Current Genetic Medicine Reports · doi:10.1007/s40142-020-00184-w · Cited by 9
Li, H., Zhou, J., Yue, Z., Feng, L., Luo, Z., Chen, S., Yang, X., & Xiao, B. (2017) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2017.09.016 · Cited by 12
Lipoprotein Metabolism, Protein Aggregation, and Alzheimer’s Disease: A Literature Review
Grao‐Cruces, E., Claro, C., la Paz, S. M., & Nóbrega, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032944 · Cited by 15
Dysregulation of neuroproteasomes by ApoE isoforms drives endogenous Tau aggregationPreprint
Paradise, V., Sabu, M., Bafia, J., Sharif, N., Nguyen, C., Konrad-Vicario, K., Mukim, R. D., Wang, X., Corjuc, B., Fu, J. M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.29.518293 · Cited by 10
Nussbaumer, J., Barve, A., Zufferey, V., Espourteille, J., Kirabali, T., Konietzko, U., Razansky, D., Rominger, A., Nordberg, A. K., Buée, L., et al. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00508-2 · Cited by 11
“APOE ε4 is the strongest genetic risk factor for sporadic AD and has been implicated in synaptic dysfunction in cellular and animal models [76].”
Perks, C. M., Barker, R. M., Alhadrami, M., Alkahtani, O., Gill, E., Grishaw, M., Harland, A. J., Henley, P., Li, H., O’Sullivan, E., et al. (2025) · Genes · doi:10.3390/genes16030331 · Cited by 11
Minati, L., Sparacino, L., Faes, L., Ito, H., Li, C., Valdes-Sosa, P. A., Frasca, M., & Boccaletti, S. (2024) · Chaos Solitons & Fractals · doi:10.1016/j.chaos.2024.115567 · Cited by 11
Raman, S., Srinivasan, G. R., Brookhouser, N., Nguyen, T., Henson, T., Morgan, D., Cutts, J., & Brafman, D. A. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c00067 · Cited by 11
Extra-Hippocampal Learning Deficits in Young Apolipoprotein E4 Mice and Their Synaptic Underpinning
Har-Paz, I., Roisman, N., Michaelson, D. M., & Moran, A. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190564 · Cited by 8
Hua, L., Gao, F., Xia, X., Guo, Q., Zhao, Y., Huang, S., & Yuan, Z. (2023) · Communications Biology · doi:10.1038/s42003-023-04952-6 · Cited by 9
“…of imaging and neuropathology studies tended to suggest some distinct aspects of pathophysiology in elderly people with different APOE genotypes 3,24 , it is still unclear whether different functional connectivity could result in distinct neuropsychological representations in elderly people…”
Mampay, M., Velasco‐Estevez, M., Rolle, S. O., Chaney, A. M., Boutin, H., Dev, K. K., Moeendarbary, E., & Sheridan, G. K. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.13036 · Cited by 9
Metadata
- Authors
- Lane-Donovan, C., & Herz, J.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Herz, Joachim
- ORCID
- Herz, Joachim
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 28
- Issue
- 4
- Pages
- 273-284
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC5366078
- OpenAlex
- W2568317134
- Cited by
- 157
- References
- 103
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 17 · 2023: 18 · 2022: 18 · 2021: 25 · 2020: 13 · 2019: 14 · 2018: 12 · 2017: 7
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (RF1AG053391, F30AG047799)
- National Heart, Lung, and Blood Institute (R37HL063762)
- National Institute of Neurological Disorders and Stroke (R01NS093382)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, apolipoprotein E, APOE ε4, apoE receptors, tripartite synapse, synapses, axon terminals, dendritic spines, astrocytes, neurodegeneration, late-onset Alzheimer's disease, genetic risk factors
- MeSH terms
- Reelin Protein, Alzheimer Disease, Animals, Apolipoproteins E, Disease Models, Animal, Female, Humans, Male, Synapses, Low Density Lipoprotein Receptor-Related Protein-1
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