The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index; none of the 35 sources its claims cite is checked for support yet.
Apolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
Open accessAbstract
Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid β peptide (Aβ) as senile plaques in the brain is the pathological hallmark of AD, but oligomeric, soluble forms of Aβ have been implicated as the synaptotoxic component. The apolipoprotein E ε 4 (apoE ε4) allele is known to be a genetic risk factor for developing AD. However, it is still unknown how apoE impacts the process of Aβ oligomerization. Here, we found that the level of Aβ oligomers in APOE ε4/ε4 AD patient brains is 2.7 times higher than those in APOE ε3/ε3 AD patient brains, matched for total plaque burden, suggesting that apoE4 impacts the metabolism of Aβ oligomers. To test this hypothesis, we examined the effect of apoE on Aβ oligomer formation. Using both synthetic Aβ and a split-luciferase method for monitoring Aβ oligomers, we observed that apoE increased the level of Aβ oligomers in an isoform-dependent manner (E2 < E3 < E4). This effect appears to be dependent on the ApoE C-terminal domain. Moreover, these results were confirmed using endogenous apoE isolated from the TBS-soluble fraction of human brain, which increased the formation of Aβ oligomers. Together, these data show that lipidated apoE, especially apoE4, increases Aβ oligomers in the brain. Higher levels of Aβ oligomers in the brains of APOE ε4/ε4 carriers compared with APOE ε3/ε3 carriers may increase the loss of dendritic spines and accelerate memory impairments, leading to earlier cognitive decline in AD.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
58 Own result · 38 Own interpretation · 23 Not checked yet · 9 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, the level of TBS-soluble Aβ oligomers in APOEε4/ε4 AD patient brains was significantly higher than that in APOEε3/ε3 AD patient brains.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plaincorrelational- 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.
- Rests on an assumption: The low-molecular-weight amyloid beta peptide likely reflects dimers and trimers.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Immunoprecipitation of apoE using each of two separate polyclonal antibodies (anti-apoE Ig (Calbiochem) and anti-apoE Ig (Millipore)) pulled down Aβ from these fractions (Figure 2C).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE forms HMW complex with Aβ oligomers in the brains of AD patients
plaincorrelationalSingle case- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We compared the amount of total soluble Aβ with the histochemically defined amounts of amyloid deposited in senile plaques, and found no correlation between plaque burden and levels of soluble Aβ (Figure 1D, r=−0.01, P=0.95).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plain- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also detected HMW Aβ and apoE in similar fractions from 185 kDa to 256 kDa using SEC-separated samples from the TBS-soluble fraction of an APOEε3/ε3 AD patient brain.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE forms HMW complex with Aβ oligomers in the brains of AD patients
plaincorrelationalSingle case- 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.
- Rests on an assumption: ApoE is secreted in high-density lipoprotein particles in the brain.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that fractions eluting from 94 kDa to 217 kDa strongly exhibited 4 kDa Aβ (hereafter called high-molecular weight (HMW) Aβ) and fractions eluting from 8.6 kDa to 16 kDa also exhibited 4 kDa Aβ (hereafter low-molecular weight (LMW) Aβ).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
boostedSingle case- 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.
- Rests on an assumption: The 4 kDa band corresponds to monomeric amyloid beta peptide under the denaturing conditions used.
- Rests on an assumption: The 8 kDa band corresponds to SDS-stable amyloid beta peptide dimers.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“6.9 times higher than that in APOEε2/εx AD patient brains”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plaincorrelational- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Remarkably, we found that the TBS-soluble fraction from APOEε4/ε4 AD patient brains exhibited substantially higher amounts of Aβ in every peak compared to APOEε3/ε3 AD patient brains.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plaincorrelational- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We measured the concentration of apoE in TBS-soluble fraction from the brains of control and AD cases by specific ELISA and found that it is similar among control and AD cases regardless of genotypes (Figure 1E).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plain- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found that Aβ eluted into fractions from 100 kDa to 200 kDa as HMW Aβ, fractions around 90 kDa, fractions around 30 kDa and fractions from 6 kDa to 20 kDa (the latter LMW Aβ, likely reflecting Aβ dimers and Aβ trimers.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plain- 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.
- Rests on an assumption: The low-molecular-weight amyloid beta peptide likely reflects dimers and trimers.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that Aβ and apoE eluted in identical fractions, ranging from 185 kDa to 256 kDa, suggesting that HMW Aβ may interact with apoE on the HDL particles.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE forms HMW complex with Aβ oligomers in the brains of AD patients
hedgedcorrelationalSingle case- 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.
- Rests on an assumption: ApoE is secreted in high-density lipoprotein particles in the brain.
- It may state two separate claims as one. 32
- Probably not a substantial claim. 18
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that the measured concentration of Aβ in HMW fractions dramatically increased, while the levels of Aβ in LMW fractions exhibited no difference (Figure 2A)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE forms HMW complex with Aβ oligomers in the brains of AD patients
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, endogenous apoE extracted from TBS-soluble fraction of human AD and control brains also increased Aβ oligomers, again apoE3 < apoE4”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that apoE2 NTF, apoE3 NTF or apo4 NTF did not enhance the luminescence”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
plain- 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 result the paper reports from its own data — 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 study, we demonstrate that the levels of Aβ oligomers in TBS-soluble fraction of AD APOEε4/ε4 brains are 2.7-fold higher compared to APOEε3/ε3 patient brains and 6.9-fold higher compared to APOEε2/εx patient brains, whereas brains from non-demented controls had negligible levels of Aβ oligomers”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that apoE4 R61T increased the level of Aβ oligomers to the same extent as apoE3, but not as high as apoE4”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that apoE3 Δ243-272, apoE3 Δ273-299 and apoE3 Δ243-299 significantly decreased the level of luminescence compared to full-length apoE3”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also found that Aβ and apoE co-eluted into HMW fractions in SEC-separated TBS-soluble fraction from AD brains, and co-immunoprecipitated”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
plaincorrelational- 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, apoA-I and apoJ/clusterin also enhance the luminescence, although to a lesser extent than apoE3”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoA-I and apoJ/clusterin also enhanced Aβ oligomerization
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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that apoE4 significantly increased the level of HMW putative 24~36 mer oligomers (or complexes of Aβ with other proteins) and decreased the level of dimers”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ApoE4 significantly increased the luminescence to a greater extent than apoE2 and apoE3, and apoE3 significantly increased the luminescence to a greater extent than apoE2”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We separated the TBS-extract of human brain by SEC and found both apoE and HMW Aβ oligomers are eluted into fraction 7 and 8 (Figure 2B).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > Human brain apoE promoted Aβ oligomerization
plain- 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“about 6.5% of LMW Aβ instead elutes in the HMW Aβ fraction (Figure 3D, 6.5 ± 0.3% with apoE, 0.5 ± 0.7 without apoE), an increase of over 10-fold.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > Purified apoE on HDL particles enhances synthetic Aβ1-42 oligomer formation in vitro
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.
A result the paper reports from its own data — 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 addition to apoE, we found apoJ/clusterin and apoA-I, other apolipoproteins on the HDL particles, increased the level of Aβ oligomers (Figure 5).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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
“Previous studies have revealed that apoE interacts with Aβ in vitro (Strittmatter et al., 1993b; LaDu et al., 1994) and in vivo, both in the cerebrospinal fluid (Strittmatter et al., 1993a) and in the brain (Näslund et al., 1995).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Introduction
What the sources say
- Not checked yetcites Strittmatter et al., 1993b
- Not checked yetcites LaDu et al., 1994 source
- Not checked yetcites Strittmatter et al., 1993a
plaincorrelational- 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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“in APP transgenic mice expressing apoE2, E3, and E4, apoE4 significantly slows Aβ clearance relative to E2 and E3 but has no effect on Aβ synthesis (Castellano et al., 2011).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Introduction
What the sources say
- Not checked yetcites Castellano et al., 2011
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
“Apolipoprotein E (apoE) is a known Aβ binding protein and is a genetic risk factor for AD (Bu et al., 2009).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Introduction
What the sources say
- Not checked yetcites Bu et al., 2009
plaincorrelational- 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.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, we assessed oligomerization using two preparations: synthetic Aβ and a quantitative split-luciferase assay, with confirmatory results.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
plain- 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.
Probably not a substantial claim.
In the paper
“ApoE has a receptor-binding domain in the amino-terminal region and a lipid-binding domain in the carboxy-terminal region (Figure 6A, Chou et al., 2005).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
What the sources say
- Not checked yetcites Chou et al., 2005
plain- 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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“We previously demonstrated that the split-luciferase tagged Aβ oligomers consist of high-molecular weight (HMW) 24~36 mer and low-molecular weight dimers by SEC analyses (Hashimoto et al., 2011).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
What the sources say
- Not checked yetcites Hashimoto et al., 2011
boosted- 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.
Probably not a substantial claim.
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
“suggesting that the apoE and Aβ HMW complex endogenously exists in the brain and is not a product caused during the mechanical homogenization steps.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
hedged- 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
“In an in vitro Aβ fibrillization assay, apoE is known to inhibit Aβ fibrillization especially in the seeding phase of Aβ fibrillization (Evans et al., 1995; Naiki et al., 1997).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > Purified apoE on HDL particles enhances synthetic Aβ1-42 oligomer formation in vitro
What the sources say
- Not checked yetcites Evans et al., 1995
- Not checked yetcites Naiki et al., 1997
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.
Probably not a substantial claim.
In the paper
“Because it is known that the level of senile plaque density in APOEε4/ε4 carrier AD is on average significantly higher than that in APOEε3/ε3 carrier AD (Rebeck et al 1993)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
What the sources say
- Not checked yetcites Rebeck et al 1993
boostedcorrelational- 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.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The current view of AD pathophysiology emphasizes the deleterious effects of Aβ oigomers on synapses, leading to synaptic dysfunction, and progressive memory impairment in AD patients (Lesné et al., 2006; Shankar et al., 2008; Li et al., 2009; Wu et al., 2010).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
What the sources say
- Not checked yetcites Lesné et al., 2006
- Not checked yetcites Shankar et al., 2008
- Not checked yetcites Li et al., 2009
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.
Probably not a substantial claim. 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
“This result may suggest that lipidated apoE enhanced the oligomerization of Aβ or stabilized the Aβ oligomers.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > Purified apoE on HDL particles enhances synthetic Aβ1-42 oligomer formation in vitro
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.
In the paper
“Although HEK293 cells transfected with human apoE3 and apoE4 naturally secrete apoE lipoparticles into the culture media (LaDu et al., 2006)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
What the sources say
- Not checked yetcites LaDu et al., 2006
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“these data were not revealed during subsequent biochemical assays.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Materials and Methods > Brain extraction and gel filtration
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.
None of the sources cited for this claim have been checked yet.
In the paper
“ApoE2 and apoE3 prefer an open-conformation, whereas apoE4 prefers a closed-conformation due to a difference at amino acid residue 112 between apoE4 (Arg) and apoE2, E3 (Cys) (Dong et al., 1994; Mahley et al., 2009)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
What the sources say
- Not checked yetcites Dong et al., 1994 source
- Not checked yetcites Mahley et al., 2009
plaincorrelational- 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
“indirectly this changes a salt bridge and alters the domain-domain interactions of the amino and carboxyl halves of apoE.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
What the sources say
- Not checked yetcites Dong et al., 1994 source
- Not checked yetcites Mahley et al., 2009
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.
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
“These data suggest that apoE, especially apoE4, impacts Aβ oligomer levels by enhancing their formation and stabilizing them once formed.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Introduction
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
“as this region may act to help catalyze oligomer formation.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
hedgedconditional- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In immunoblotting, we confirmed the expression of these apoE fragments using anti-human apoE antibodies.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
plain- 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.
Probably not a substantial claim.
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
“This suggests that the carboxy-terminal region of apoE is necessary and sufficient to induce Aβ oligomerization.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Selected brains also had a similar age at death, gender ratio, disease duration and similar postmortem interval (Table 1).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > APOEε4/ε4 AD patients have higher levels of Aβ oligomers in their brain than APOEε3/ε3 or APOEε2/εx AD patients
plain- 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
“These qualitative and quantitative data suggest that lipidated apoE enhances Aβ oligomerization and inhibited further aggregation in vitro.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > Purified apoE on HDL particles enhances synthetic Aβ1-42 oligomer formation in vitro
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The carboxy-terminal domain of apoE contains the major lipid-binding region (243-272 amino acid residues) (Hatters et al., 2006; Mahley et al., 2009).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > The lipid-binding domain of apoE is necessary for enhancement of Aβ oligomerization
What the sources say
- Not checked yetcites Hatters et al., 2006
- Not checked yetcites Mahley et al., 2009
plain- 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.
Probably not a substantial claim.
In the paper
“These immortalized astrocyte cells are known to secrete human apoE’s in HDL-like particles into conditioned media (Morikawa et al., 2005).”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > Purified apoE on HDL particles enhances synthetic Aβ1-42 oligomer formation in vitro
What the sources say
- Not checked yetcites Morikawa et al., 2005
boosted- 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.
Probably not a substantial claim.
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
“Our results suggest that apoE4 increases the level of Aβ oligomers in the brain, leading to increased synaptic localization with Aβ oligomers, synaptic dysfunction and hastening the development of cognitive impairments.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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
“supporting the idea that apoE lipidation may be critical to facilitate Aβ oligomer formation.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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.
Probably not a substantial claim.
In the paper
“apoJ/clusterin deficient mice crossed with APP transgenic mice exhibit significantly fewer fibrillar Aβ deposits in the brain compared to APP transgenic mice (DeMattos et al., 2002)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoA-I and apoJ/clusterin also enhanced Aβ oligomerization
What the sources say
- Not checked yetcites DeMattos et al., 2002
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.
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
“suggesting that lipidated apoE, especially apoE4 might stabilize Aβ oligomers and inhibit the dissociation or further aggregation of Aβ.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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
“Recently it was reported that the level of soluble oligomeric Aβ in frontal cortex of young adults is higher than that of elderly people or Alzheimer’ disease patients using ELISA experiments (Halmond et al., 2010)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
What the sources say
- Not checked yetcites Halmond et al., 2010
plaincorrelational- 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.
Probably not a substantial claim.
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 small or no effect of apoA-I on Aβ oligomerization and fibrillization.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
hedged- 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
“Common variants in the apoJ/clusterin gene (CLU) have recently been linked to an increased risk of developing AD (Harold et al., 2009; Lambert et al., 2009)”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
What the sources say
- Not checked yetcites Harold et al., 2009
- Not checked yetcites Lambert et al., 2009
plaincorrelational- 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
“Thus, these results indicate that apoE influences both plaque burden and also the levels of TBS-soluble Aβ oligomers in an isoform-differential manner.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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
“Interestingly, experiments using deletion mutants of apoE demonstrate that the carboxy-terminal domain of apoE is necessary and sufficient to drive Aβ oligomerization, suggesting that apoE may directly interact with Aβ oligomers through its carboxy-terminal region”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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
“and that apoE, particularly apoE4, promotes and stabilizes Aβ oligomerization.”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Discussion
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.
The paper relies on this without support.
It is still unknown what factors influence the kinetics of formation of soluble amyloid beta peptide oligomers.
“However, it is still unknown what factors influence the kinetics of formation of soluble Aβ oligomers.”
The paper relies on this without support.
Whether apoE increases the levels of native amyloid beta peptide oligomers remains unknown.
“However, because of the difficulty in monitoring Aβ oligomers specifically and quantitatively, whether apoE increases the levels of native Aβ oligomers remains unknown.”
The paper relies on this without support.
ApoE is secreted in high-density lipoprotein particles in the brain.
“ApoE is secreted in high-density lipoprotein (HDL) particles in the brain.”
The paper relies on this without support.
The 4 kDa band corresponds to monomeric amyloid beta peptide under the denaturing conditions used.
“a 4 kDa band, corresponding (under these denaturing conditions) to monomeric Aβ”
The paper relies on this without support.
The 8 kDa band corresponds to SDS-stable amyloid beta peptide dimers.
“an 8 kDa band corresponding to SDS-stable Aβ dimers”
The paper relies on this without support.
The low-molecular-weight amyloid beta peptide likely reflects dimers and trimers.
“the latter LMW Aβ, likely reflecting Aβ dimers and Aβ trimers.”
The paper relies on this without support.
ApoA-I, apoA-II, and apoJ/clusterin are present on HDL particles in the brain.
“Besides apoE, apoA-I, apoA-II and apoJ/clusterin are also present on the HDL particles in the brain.”
The paper relies on this without support.
APOEε4 inheritance is a major risk factor for Alzheimer's disease.
“the major risk for AD associated with APOEε4 inheritance.”
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
“Aβ42 aggregation was highest in the presence of human ApoE3 protein (C-terminus domain), lower in the presence of human ApoE3ch (similar to that observed in the presence of ApoE213), and lowest in the absence of any ApoE (Extended Data 3).”
From Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report (2019) · cites this paper as [13]
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
“The literature suggests that there are isoform-dependent differences in ApoE–plaque associations but that several factors, such as ApoE lipidation state, compartment or cell type of origin, and Aβ conformational state, also have important roles in ApoE–Aβ interactions52–56.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [56]
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
“Several recent studies provided evidence to support increased content of Ab oligomers in the extracellular space in brains of patients with AD, expressing the human ApoE4 isoform, 37,38 and intraneuronally in mice expressing human ApoE4 isoform after inhibition of Ab-degrading enzyme neprilysin.39”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [37]
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
“and the increased propensity of Aβ to oligomerize in the presence of APOE4 is considered a major mechanism by which APOE4 increases AD risk113–116 (Fig. 2c).”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [113]
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
“APOE4 is associated with increased oligomerization and deposition of Aβ in vitro and in vivo113,115,192”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [113]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“This finding was confirmed using a split-luciferase complementation assay sensitive to the characterization of potentially neurotoxic Aβ42 oligomers13.”
From Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report (2019) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This finding also aligns with evidence that Aβ oligomer levels in APOE4 AD patients’ brains are 2.7 times higher than those in APOE3 AD patients [73]”
The cited source says what the claim attributes to it.
In the citing paper
“It has been recently appreciated that apoE, especially its apoE4 isoform, facilitates the formation of Aβ oligomers [33,34].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [33]
The cited source says what the claim attributes to it.
In the citing paper
“Although it appears that enhanced Aβ oligomerization occurs in settings of elevated Aβx-42 level, which is associated with the apoE4 background, there is experimental evidence to indicate that direct interaction between apoE and Aβ facilitates Aβ oligomeric assembly and that all three isoforms promote this process in the rank order E4 > E3 > E2 [33].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
“ApoE2 and apoE3 prefer an open-conformation, whereas apoE4 prefers a closed-conformation”
§ Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide > Results > ApoE enhances the level of Aβ oligomers in an isoform dependent manner (apoE2 < apoE3 < apoE4)
“the apoE4 R61T mutation, which is known to change the apoE4 conformation so that it mimics the closed apoE3 conformation”
Citations
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 4×
“The current view of AD pathophysiology emphasizes the deleterious effects of A oligomers on synapses, leading to synaptic dysfunction, and progressive memory impairment in AD patients (Lesné et al., 2006; Shankar et al., 2008; Li et al., 2009; Wu et al., 2010).”
BackgroundInfluentialRetractedCorder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234
Alzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424
Self-citationStrittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,242 · cited 1×
“Importantly, it has now been shown that in APP-transgenic mice expressing apoE2, E3, and E4, apoE4 significantly slows A clearance relative to E2 and E3 but has no effect on A synthesis (Castellano et al., 2011).”
BackgroundSelf-citation
Cited by
Sorted by citations
Items 101–108 of 108
Extracellular Proteolysis of Apolipoprotein E (apoE) by Secreted Serine Neuronal Protease
Tamboli, I. Y., Heo, D., & Rebeck, G. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093120 · Cited by 35
APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer’s disease
Brookhouser, N., Raman, S., Frisch, C., Srinivasan, G., & Brafman, D. A. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01076-3 · Cited by 33
Opposing 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
Self-citationHigh-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22
Kara, E., Marks, J. D., Roe, A. D., Commins, C., Fan, Z., Calvo-Rodriguez, M., Wegmann, S., Hudry, E., & Hyman, B. T. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001388 · Cited by 20
Self-citationGolden, L. R., Siano, D. S., Stephens, I. O., MacLean, S. M., Saito, K., Nolt, G. L., Funnell, J. L., Pallerla, A. V., Lee, S., Smith, C., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02094-y · Cited by 18
Pankiewicz, J. E., Lizińczyk, A. M., Franco, L. A., Diaz, J. R., Martá-Ariza, M., & Sadowski, M. J. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01261-z · Cited by 15
Yesiltepe, M., Yin, T., Tambini, M., Bao, H., Pan, M., d’Abramo, C., Giliberto, L., Han, X., & D’Adamio, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01832-2 · Cited by 10
“This finding also aligns with evidence that Aβ oligomer levels in APOE4 AD patients’ brains are 2.7 times higher than those in APOE3 AD patients [73] and is consistent with findings from mouse models expressing APOE4 and APOE2 [74].”
ResultInfluential
Metadata
- Authors
- Hashimoto, T., Serrano-Pozo, A., Hori, Y., Adams, K. W., Takeda, S., Banerji, A. O., Mitani, A., Joyner, D., Thyssen, D. H., Bacskai, B. J., Frosch, M. P., Spires-Jones, T. L., Finn, M. B., Holtzman, D. M., & Hyman, B. T.
- Affiliations
- Massachusetts General Hospital (US)
- Washington University in St. Louis (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-10-24
- Volume
- 32
- Issue
- 43
- Pages
- 15181-15192
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3493562
- OpenAlex
- W1966895399
- Cited by
- 294
- References
- 44
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 24 · 2023: 15 · 2022: 32 · 2021: 29 · 2020: 22 · 2019: 30 · 2018: 16 · 2017: 20 · 2016: 7 · 2015: 17 · 2014: 23 · 2013: 16 · 2012: 1
- FWCI
- 12.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health
- Japan Society for the Promotion of Science (24800015)
- National Institute on Aging (R01AG013956, RC1AG036265, R00AG033670, AG 12406, R37AG012406, AG033670, P50AG005134, R37AG013956, AG13956, K99AG033670, P30AG062421, R01AG012406)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE ε4, amyloid-beta, Alzheimer's disease, APOE isoforms, dendritic spine loss, memory impairment, genetic risk factors
- MeSH terms
- Alzheimer Disease, Analysis of Variance, Astrocytes, Brain, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Peptide Fragments, Transfection, Amyloid beta-Peptides, Protein Isoforms, Green Fluorescent Proteins, Lipid Metabolism, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2, HEK293 Cells, Morpholinos
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-01, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-01 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
