Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
Open accessAbstract
The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for the development of Alzheimer's disease (AD). Accumulation of amyloid-β (Aβ) is hypothesized to initiate synaptic and neuronal dysfunction that ultimately lead to neuronal cell death in AD, and several lines of
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Written from the paper’s full text.
TL;DR
This review/commentary discusses Dumanis et al. (2009), which reported that APOE4-targeted replacement mice have fewer cortical dendritic spines than APOE2 or APOE3 mice, with isoform-dependent spine length differences. It argues that in vivo spine dynamics, spine subtype identity, and apoE protein levels remain unresolved and require further study.
Key findings
- In Dumanis et al. (2009), APOE4 mice had significantly fewer dendritic spines in layer II/III cortical pyramidal neurons than APOE2 or APOE3 mice at all ages examined; no cortical spine density difference was observed between APOE2 and APOE3 mice.
- Spine length differed by isoform: at 1 month of age, APOE2 mice had longer cortical spines than APOE3 and APOE4 mice; in the 1-year-old cohort, APOE4 mice had shorter spines than APOE2 and APOE3 mice.
- No differences in hippocampal spine density were found among mice expressing different human APOE isoforms; the presence of any human apoE isoform increased spine number at 3 months of age compared with mice lacking apoE.
- The review notes that whether apoE4 represents a gain of toxic function or loss of neuroprotective function remains debated; the spine data lend some support to the latter, but APOE-null mice were not included in the 1-year-old cohort.
Methods
- Design: review/commentary evaluating Dumanis et al. (2009); no new primary data are presented.
- Data/sample: Dumanis et al. used Golgi impregnation in mice in which human APOE2, APOE3, or APOE4 was substituted into the mouse APOE locus, plus apoE-null mice, across multiple ages and brain regions.
- Main analysis: narrative synthesis of reported dendritic spine density and morphology findings; no meta-analysis or new statistical analysis is described.
Limitations
- Stated in the review: the Golgi technique quantified spine number at a single time point, so it cannot distinguish decreased spine formation from increased elimination; the analysis did not distinguish spine subtypes; APOE-null mice were not included in the 1-year-old cohort; different apoE protein levels among isoforms could account for the findings; and functional synaptic activity was not analyzed.
- Evident from the text: this is a review/commentary rather than a primary experimental test, and conclusions about human brain relevance and AD pathogenesis remain speculative; the review calls for two-photon imaging and APOE-isoform mice expressing human Aβ to test whether effects persist during AD pathogenesis.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Claims the paper makes
13 of 19 cited sources checked · 12 supported · 0 flagged · accuracy not yet measured
- Premisenone given§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
The study by Dumanis et al. (2009) is the first to systematically compare dendritic spines in vivo in mice in which the human APOE2, APOE3, or APOE4 gene has been substituted into the mouse APOE locus.
“The study by Dumanis et al. (2009) is the first to systematically compare dendritic spines in vivo in mice in which the human APOE2, APOE3, or APOE4 gene has been substituted into the mouse APOE locus.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
Several lines of evidence strongly suggest that the differential effects of apoE isoforms on Aβ aggregation and/or clearance plays a major role in AD pathogenesis.
“several lines of evidence strongly suggest that the differential effects of apoE isoforms on A aggregation and/or clearance plays a major role in AD pathogenesis (Kim et al., 2009).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Kim et al., 2009 source
- Rests on an assumption: The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for the development of Alzheimer's disease (AD).
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
No differences in cortical spine density between APOE2 and APOE3 mice were observed.
“No differences in cortical spine density between APOE2 and APOE3 mice were observed [Dumanis et al. (2009), their Fig. 1, Fig. 3].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
Spine length differed between mice expressing different APOE isoforms.
“Dumanis et al. (2009) also found that spine length differed between mice expressing different APOE isoforms.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
At all ages examined, mice expressing APOE4 had significantly fewer dendritic spines in layer II/III cortical pyramidal neurons than mice expressing APOE2 or APOE3.
“One of the principal findings was that, at all ages examined, mice expressing APOE4 had significantly fewer dendritic spines in layer II/III cortical pyramidal neurons than mice expressing APOE2 or APOE3 [Dumanis et al. (2009), their Fig. 1, Fig. 3].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
At 1 month of age, APOE2 mice had longer cortical spines than APOE3 and APOE4 mice.
“At 1 month of age, APOE2 mice had longer cortical spines than APOE3 and APOE4 mice [Dumanis et al. (2009), their Fig. 1 F-H].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
In the 1-year-old cohort, the mice expressing the APOE4 gene had shorter spines than APOE2 and APOE3 mice.
“In the 1-year-old cohort, the mice expressing the APOE4 gene had shorter spines than APOE2 and APOE3 mice [Dumanis et al. (2009), their Fig.3H].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
A recent study by Korwek et al. (2009) did not find a difference in apoE protein levels in the hippocampus of mice expressing different human APOE isoforms.
“However, a recent study by Korwek et al. (2009) did not find a difference in apoE protein levels in the hippocampus of mice expressing different human APOE isoforms.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Korwek et al., 2009 source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
An increase in the levels of Aβ secreted from axons and dendrites decreases spine number significantly in local dendrites.
“Recently, it was demonstrated that an increase in the levels of A secreted from axons and dendrites decreases spine number significantly in local dendrites (Wei et al., 2010).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Wei et al., 2010 source
- Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
The presence of any human apoE isoform led to increased spine number at 3 months of age in comparison to mice that lack apoE.
“They compared dendritic spine number and length between neurons from mice lacking apoE altogether and mice in which a human APOE isoform replaced the mouse APOE gene, and demonstrated that the presence of any human apoE isoform led to increased spine number at 3 months of age in comparison to mice that lack apoE [Dumanis et al. (2009), their Fig.3A-C].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Dumanis et al. (2009) source
The Results section on 4-week-old mice (Fig. 1C–E; page not provided) reports greater cortical spine density in APOE2 and APOE3 replacement mice than in apoE-deficient mice, but says APOE4 mice had similarly reduced density to mice lacking apoE. The 3-month Results (Fig. 3A–C; page not provided) compare the three human isoforms with one another, not with apoE-deficient mice. Thus, the paper does not establish the claimed increase for every isoform at 3 months. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Interpretationnone given§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
The technique used by Dumanis et al. (2009) only allowed quantification of spine number at a single time point.
“The technique used by Dumanis et al. (2009) only allowed quantification of spine number at a single time point.”
Quote in the paperSubstantial claim - Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
Spine density reflects the balance between spine formation and elimination.
“However, spine density reflects the balance between spine formation and elimination (Alvarez and Sabatini, 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Alvarez and Sabatini, 2007 source
- Interpretationcitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
The data presented by Dumanis et al. (2009) lends some support to the hypothesis that the presence of apoE4 represents a loss of a neuroprotective function, at least in regard to dendritic spine morphology.
“The data presented by Dumanis et al. (2009) lends some support to the latter hypothesis, at least in regard to dendritic spine morphology.”
Quote in the paperSubstantial claim - Interpretationown data§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
The APOE isoforms differentially modulate dendritic spine number and morphology in vivo in the otherwise normal mouse brain.
“In summary, it appears that the APOE isoforms differentially modulate dendritic spine number and morphology in vivo in the otherwise normal mouse brain.”
Quote in the paperSubstantial claim- Rests on an assumption: The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for the development of Alzheimer's disease (AD).
- Rests on an assumption: Dendritic spines play an important role in synapse function as the site of excitatory glutamatergic synaptic input.
- Classified as probably not a substantial claim. 13
- May combine two claims. 6
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsBoth formation and elimination of spine are associated with learning and could play a role in memory formation.
“However, more recent two-photon studies demonstrated that both formation and elimination of spine are associated with learning and could play a role in memory formation (Xu et al., 2009;Yang et al., 2009).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites Xu et al., 2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Yang et al., 2009 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsThe effect of apoE isoforms on dendrite structure and function has been extensively investigated in vitro with widely differing results depending on a variety of factors.
“The effect of apoE isoforms on dendrite structure and function has been extensively investigated in vitro with widely differing results depending on a variety of factors (Kim et al., 2009).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Kim et al., 2009 source
May combine two claims.
Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsThe amount of apoE protein in the brain differs among mice expressing different human isoforms, with the highest levels in APOE2 mice and the lowest in APOE4 mice.
“Several studies have shown that the amount of apoE protein in the brain differs among mice expressing different human isoforms, with the highest levels in APOE2 mice and the lowest in APOE4 mice (Kim et al., 2009).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Kim et al., 2009 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsSynapse connectivity during experience-dependent processes could predominantly be shaped by the extent of spine loss.
“This finding suggests that synapse connectivity during experience-dependent processes could predominantly be shaped by the extent of spine loss.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsIt is possible that the decreased spine density in older APOE4 mice results from increased spine elimination.
“Because the addition of a new stable spine is a rare event in adult mice (Alvarez and Sabatini, 2007), it is possible that the decreased spine density in older APOE4 mice results from increased spine elimination.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Alvarez and Sabatini, 2007 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsLong-term sensory deprivation dramatically reduced spine elimination, but had no effect on spine formation.
“The authors found that long-term sensory deprivation dramatically reduced spine elimination, but had no effect on spine formation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zuo et al., 2005 source
Classified as probably not a substantial claim. May combine two claims.
Interpretationreasoning§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsThe decreased number of cortical spines in APOE4 mice could be caused by a decrease in spine formation and/or an increase in elimination.
“Therefore, the decreased number of cortical spines in APOE4 mice could be caused by a decrease in spine formation and/or an increase in elimination.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsMushroom spines represent more stable synaptic connections (memory spines), whereas thin spines are more dynamic and respond to changes in synaptic connections (learning spines).
“It has been proposed that mushroom spines represent more stable synaptic connections (memory spines), whereas thin spines are more dynamic and respond to changes in synaptic connections (learning spines) (Bourne and Harris, 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bourne and Harris, 2007 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsYoung mice have many long, thin dendritic protrusions known as filopodia, which may be spine precursors.
“Young mice have many long, thin dendritic protrusions known as filopodia, which may be spine precursors (Alvarez and Sabatini, 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Alvarez and Sabatini, 2007 source
Classified as probably not a substantial claim.
Interpretationreasoning§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsIt is difficult to conclude that the structural differences observed between isoforms actually represent variations in synaptic strength and integrity, because the authors did not distinguish between spine subtypes in their analysis.
“However, it is difficult to conclude that the structural differences observed between isoforms actually represent variations in synaptic strength and integrity, because the authors did not distinguish between spine subtypes in their analysis.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Interpretationreasoning§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsIt is premature to conclude that the lower spine density in the APOE4 mice represents the loss of a neuroprotective function.
“However, APOE-null mice were not included in the 1-year-old cohort, so it is premature to conclude that the lower spine density in the APOE4 mice represents the loss of a neuroprotective function.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).
Interpretationcitation§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsThe different levels of apoE protein could account for the differences observed between isoforms in their study.
“As Dumanis et al. (2009) point out, the different levels of apoE protein could account for the differences observed between isoforms in their study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone given§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsWhether these structural differences reflect functional changes in synaptic activity was not analyzed.
“Whether these structural differences reflect functional changes in synaptic activity was not analyzed.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning§ Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic AlterationsIt is possible that the differential effects of the APOE isoforms on dendritic spine may be altered or absent in the presence of high Aβ levels.
“As a result, it is possible that the differential effects of the APOE isoforms on dendritic spine may be altered or absent in the presence of high A levels.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for the development of Alzheimer's disease (AD).
“The 4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for the development of Alzheimer's disease (AD).”
The paper relies on this without support.
Dendritic spines play an important role in synapse function as the site of excitatory glutamatergic synaptic input.
“Dendritic spines, small protrusions along the length of the dendrite, play an important role in synapse function as the site of excitatory glutamatergic synaptic input.”
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?
A hallmark of the ApoE4 mouse phenotype is reduced neuronal complexity, characterized by fewer, shorter, and less branched dendrites, including reduced dendritic spine density in the hippocampus and entorhinal cortex.
“A hallmark of the ApoE4 mouse phenotype is reduced neuronal complexity, characterized by fewer, shorter, and less branched dendrites. This includes a major reduction in dendritic spine density in the hippocampus (specifically the dentate gyrus and CA1 regions) and the entorhinal cortex [26–28].”
From Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice (2026) · cites this paper as [27]
In its discussion of Dumanis et al. (2009) (page unavailable), the paper reports fewer spines in APOE4 cortical neurons and shorter cortical spines in one-year-old APOE4 mice. It also explicitly reports no difference in hippocampal spine density among the APOE isoforms. The copy does not establish the claimed reduction in the dentate gyrus, CA1, or entorhinal cortex, or that the dendrites themselves were fewer and shorter. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThere is an association between the apoE4 and spine deficits in vivo.
“Other previous studies also reported an association between the apoE4 and spine deficits in vivo (Basak and Kim, 2010; Dumanis et al., 2009; Ji et al., 2003; Wang et al., 2005).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Basak and Kim, 2010
Cites
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · cited 4× · see citing works
“The effect of apoE isoforms on dendrite structure and function has been extensively investigated in vitro with widely differing results depending on a variety of factors (Kim et al., 2009).”
BackgroundInfluentialSelf-citationRapid formation and selective stabilization of synapses for enduring motor memories
Xu, T., Yu, X., Perlik, A. J., Tobin, W. F., Zweig, J. A., Tennant, K., Jones, T., & Zuo, Y. (2009) · Nature · doi:10.1038/nature08389 · Cited by 1,193 · cited 1× · see citing works
“However, more recent two-photon studies demonstrated that both formation and elimination of spine are associated with learning and could play a role in memory formation (Xu et al., 2009; Yang et al., 2009).”
BackgroundStably maintained dendritic spines are associated with lifelong memories
Yang, G., Pan, F., & Gan, W.-B. (2009) · Nature · doi:10.1038/nature08577 · Cited by 1,182 · cited 1× · see citing works
“However, more recent two-photon studies demonstrated that both formation and elimination of spine are associated with learning and could play a role in memory formation (Xu et al., 2009; Yang et al., 2009).”
BackgroundDo thin spines learn to be mushroom spines that remember?
Bourne, J., & Harris, K. M. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.04.009 · Cited by 843 · cited 1× · see citing works
“It has been proposed that mushroom spines represent more stable synaptic connections (memory spines), whereas thin spines are more dynamic and respond to changes in synaptic connections (learning spines) (Bourne and Harris, 2007).”
BackgroundAnatomical and Physiological Plasticity of Dendritic Spines
Alvarez, V. A., & Sabatini, B. L. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094222 · Cited by 629 · cited 3× · see citing works
“Because the addition of a new stable spine is a rare event in adult mice (Alvarez and Sabatini, 2007), it is possible that the decreased spine density in older APOE4 mice results from increased spine elimination.”
BackgroundInfluentialLong-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex
Zuo, Y., Yang, G., Kwon, E., & Gan, W.-B. (2005) · Nature · doi:10.1038/nature03715 · Cited by 436 · cited 1× · see citing works
“A previous study using two-photon microscopy to measure spine turnover in the living mouse brain analyzed spine formation and elimination following a decrease in barrel cortex activity due to sensory deprivation (Zuo et al., 2005).”
Amyloid beta from axons and dendrites reduces local spine number and plasticity
Wei, W., Nguyen, L. N., Kessels, H. W., Hagiwara, H., Sisodia, S., & Malinow, R. (2010) · Nature Neuroscience · doi:10.1038/nn.2476 · Cited by 357 · cited 1× · see citing works
“Recently, it was demonstrated that an increase in the levels of A secreted from axons and dendrites decreases spine number significantly in local dendrites (Wei et al., 2010).”
BackgroundApoE4 Decreases Spine Density and Dendritic Complexity in Cortical Neurons<i>In Vivo</i>
Dumanis, S. B., Tesoriero, J. A., Babus, L. W., Nguyen, M. T., Trotter, J. H., Ladu, M. J., Weeber, E. J., Turner, R. S., Xu, B., Rebeck, G. W., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4026-09.2009 · Cited by 220 · cited 13× · see citing works
“In the 1-year-old cohort, the mice expressing the APOE4 gene had shorter spines than APOE2 and APOE3 mice [Dumanis et al. (2009), their Fig.”
BackgroundMethodResultInfluentialApoE isoform-dependent changes in hippocampal synaptic function
Korwek, K. M., Trotter, J. H., LaDu, M. J., Sullivan, P. M., & Weeber, E. J. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-21 · Cited by 89 · cited 1× · see citing works
“However, a recent study by Korwek et al. (2009) did not find a difference in apoE protein levels in the hippocampus of mice expressing different human APOE isoforms.”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Apolipoprotein E in Alzheimer's Disease: An Update
Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394 · see citing works
“APOE isoforms may differentially affect synaptic plasticity and dendritic spine integrity via the modulation of spine elimination (Basak & Kim 2010); as a result of isoformdependent levels of APOE (Basak & Kim 2010, Dumanis et al. 2009); and by acting as signaling molecules through interactions…”
BackgroundKim, J., Yoon, H., Basak, J., & Kim, J. (2014) · Molecules and Cells · doi:10.14348/molcells.2014.0248 · Cited by 141 · see citing works
“Other previous studies also reported an association between the apoE4 and spine deficits in vivo (Basak and Kim, 2010; Dumanis et al., 2009; Ji et al., 2003; Wang et al., 2005).”
ResultSelf-citationObisesan, T. O., Umar, U., Plauvoi, & Gillum (2012) · Clinical Interventions in Aging · doi:10.2147/cia.s26794 · Cited by 41 · see citing works
“26 Its contribution to AD risk is graded across its three known common isoforms (E2, E3, and E4) in humans encoded by ε 2, ε 3, and ε 4 alleles.”
Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
Khavinson, V. K., Ilina, A., Kraskovskaya, N., Linkova, N. S., Колчина, Н. В., Mironova, E. S., Erofeev, A., & Petukhov, M. (2021) · Pharmaceuticals · doi:10.3390/ph14060515 · Cited by 17 · see citing works
“It was established that different apoE isoforms might produce differences in synaptic structure and function that make neuronal cells more susceptible to the toxic insults that occur with AD [60].”
Yang, X., Yao, K., Zhang, M., Zhang, W., & Zu, H. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111321 · Cited by 12 · see citing works
“What ’ s more, increasing evidences show a close relationship between apoE4 and synapse injuries in in-vivo models (Ji et al., 2003; Dumanis et al., 2009; Basak and Kim, 2010).”
Hsu, C.-H., Chu, P.-W., Chen, Y.-Y., Ho, M.-H., Liao, E.-C., & Chen, S.-K. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04842-3
- Authors
- Basak, J. M., & Kim, J.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-03-31
- Volume
- 30
- Issue
- 13
- Pages
- 4526-4527
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6632298
- OpenAlex
- W1980991647
- Semantic Scholar
- ef891f1ff15411368b7b4572b2fe4e4b725484b2
- Cited by
- 6
- References
- 9
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 1 · 2014: 2 · 2012: 1
- FWCI
- 0.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- PubMed Central (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › 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
- apolipoprotein E, APOE ε4, dendritic spines, Alzheimer's disease, amyloid-beta, synaptic dysfunction, genetic risk factors, in vivo imaging, neuronal cell death
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