The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index; 13 of the 20 sources its claims cite were checked for support.
Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report
Open accessAbstract
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
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Claims the paper makes
19 Own result · 16 Own method · 10 Own interpretation · 6 No full text of the sources · 5 Supported · 3 Partly supported · 3 Couldn’t confirm · 2 No basis given · 1 Not supported · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“She had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid, and limited tau/tangle and neurodegenerative measurements.”
- Also stated in: § Abstract · plain
“Whole exome sequencing corroborated her PSEN1 E280A mutation and discovered that she had two copies of the rare Christchurch (APOEch)7 mutation (an arginine-to-serine substitution at amino acid 136, corresponding to codon 154) in APOE3.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Disputedcites [7] Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R. & Carrell, R. W. J. Clin. Invest. 80, 483–490 (1987). sourceExperimental — accuracy not yet measured
The Discussion (page not supplied) says the patient was heterozygous for apo E2-Christchurch (R136S) and apo E2 (R158C), not that the patient carried two copies of the Christchurch variant. The Results also identify the patient as J.W.T. and describe him as heterozygous; this paper does not describe the woman in the citing sentence. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plainSingle 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.
- Also stated in: § Abstract · plain
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Our analyses of heparin binding showed that ApoE4 had higher affinity for heparin compared to ApoE3 and ApoE217.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Could not verifycites [17] Aguirre-Acevedo, D. C. et al. Validez y. fiabilidad de. la batería neuropsicológica CERAD-Col. 45, 655–660 (2007). sourceExperimental — accuracy not yet measured
The available copy’s Subjects and methods and Results passages describe validation of the CERAD-Col neuropsychological battery, not heparin-binding experiments. Searches for ApoE isoforms and heparin affinity or binding found no passage addressing the comparison. (LLM, conf=0.76)
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.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“Whole genome sequencing and a Genomizer8 analysis were used to comprehensibly identify and rank all potentially significant rare and common variants, confirm the PSEN1 E280A mutation as her primary risk factor, and identify APOE3ch homozygosity as her most likely genetic modifier.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Supportedcites [8] Smedley, D. et al. Am. J. Hum. Genet. 99, 595–606 (2016). source
The citation is attached to “Genomizer,” identifying the analysis tool rather than attributing the subject’s genetic findings to this paper. The Discussion describes Genomiser as a framework for prioritizing variants from whole-genome sequences; it does not report findings about this subject. (LLM, conf=0.90)
plaindirectSingle 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“She also had relatively low plasma neurofilament light chain (NfL) measurements (20.24 pg/mL), a blood marker of axonal injury and neurodegeneration12 related to familial AD, particularly for her older age (her result and the mean and standard deviation of non-mutation carriers in the same age range, data not shown).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Supportedcites [12] Preische, O. et al. Nat. Med. 25, 277–283 (2019). sourceExperimental — accuracy not yet measured
Preische et al. (2019) supports the cited background claim: its paper-scoped snippet describes serum NfL as a biomarker of neurodegeneration in familial Alzheimer’s disease and compares mutation carriers with non-carriers (score 0.636). The 20.24 pg/mL measurement and the judgment that it was low for this woman’s age are observations made by the citing paper; its age-range comparison is explicitly marked ‘data not shown.’ Those individual-level details cannot be verified from Preische et al., but the citation reasonably supports the biomarker context rather than purporting to be their source. (LLM, conf=0.82)
plainSingle 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Whole genome sequencing and a Genomizer8 analysis were used to comprehensibly identify and rank all potentially significant rare and common variants, confirm the PSEN1 E280A mutation as her primary risk factor, and identify APOE3ch homozygosity as her most likely genetic modifier.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Supportedcites [8] Smedley, D. et al. Am. J. Hum. Genet. 99, 595–606 (2016). source
The citation is attached to the name of the analysis tool, rather than to the citing authors’ finding about their subject. The Results section (“Phenotype-Driven Prioritization of Non-coding Variants”) identifies Genomiser as a framework for prioritizing variants from whole-genome data; the subject-specific APOE3ch finding is not attributed to this source. (LLM, conf=0.87)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This finding was confirmed using a split-luciferase complementation assay sensitive to the characterization of potentially neurotoxic Aβ42 oligomers13.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Supportedcites [13] Hashimoto, T. et al. J. Neurosci. 32, 15181–15192 (2012). sourceExperimental — accuracy not yet measured
Hashimoto et al. (2012) describes the split-luciferase complementation assay and uses it to measure Aβ oligomers, supporting the citation in the verbatim sentence. Its paper-scoped snippet (score 0.749) says the assay monitors oligomers specifically and quantitatively. The ApoE3ch comparison is a result reported by the citing case report, not an experiment shown in Hashimoto et al.; the citation supports the assay, not that variant-specific finding. (LLM, conf=0.83)
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.
- Supported
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 identified a PSEN1 mutation carrier from the world’s largest autosomal dominant Alzheimer’s disease kindred who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset.”
- Also stated in: § Abstract · plain
“One mutation carrier did not develop MCI until her seventies, nearly three decades after the typical age of onset.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plainSingle 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.
- Also stated in: § Abstract · plain
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
“Luciferase luminescence by oligomer formation is significantly reduced in ApoE3ch compared to ApoE3 WT indicating lower aggregation. (*p = 0.0202, 2-tailed unpaired T-test, n=6).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Extended Data
hedgeddirectn = 6- 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 found that compared to other ApoE isoforms, ApoE3ch displayed the lowest heparin binding ability (Figure 2).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
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
“Single cell RNA sequencing of peripheral blood mononuclear cells confirmed allele-specific expression of her PSEN1 E280A mutation (Supplementary Table 2 & Supplementary Table 3).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plaindirectSingle case- 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. 20
- Probably not a substantial claim. 26
- The quote only partly states this claim. 3
Every source the paper cites for this claim was checked and supports it.
In the paper
“Whole exome sequencing corroborated her PSEN1 E280A mutation and discovered that she had two copies of the rare Christchurch (APOEch)7 mutation (an arginine-to-serine substitution at amino acid 136, corresponding to codon 154) in APOE3.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Supportedcites [7] Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R. & Carrell, R. W. J. Clin. Invest. 80, 483–490 (1987). source
The citation identifies the Christchurch variant, rather than serving as evidence for the citing authors’ sequencing result. The Results identify its arginine-to-serine substitution at residue 136, and the Discussion says that substitution can arise in the APOE3 gene. The paper does not report the woman’s PSEN1 mutation or her two copies of the variant; those are findings of the citing study. (LLM, conf=0.88)
plainSingle 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.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“HSPG has been suggested to promote Aβ aggregation and neuronal uptake of extracellular tau; and ApoE-binding may be necessary for some of these effects15,16.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Supportedcites [15] Rauch, J. N. et al. Sci. Rep. 8, 6382 (2018). sourceExperimental — accuracy not yet measured
Rauch et al. (2018) directly supports the tau-uptake part of the claim: its paper-scoped snippet reports that heparan sulfate 6-O sulfation regulates tau uptake in iPS-derived neurons (score 0.779). The retrieved passages do not establish the separate Aβ-aggregation or ApoE-binding points, which may rely on the sentence’s other citation. This is a partial attribution, not a contradiction; the prior disputed verdict is not warranted. (LLM, conf=0.82)
- Partly supportedcites [16] Yamauchi, Y. et al. Biochemistry 47, 6702–6710 (2008). sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) states that ApoE binds HSPG and links that interaction to neurite growth, repair, and Alzheimer’s disease. It does not say that HSPG promotes Aβ aggregation or neuronal uptake of extracellular tau, or that ApoE binding is necessary for either process. (LLM, conf=0.84)
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. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the 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).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Partly supportedcites [13] Hashimoto, T. et al. J. Neurosci. 32, 15181–15192 (2012). sourceExperimental — accuracy not yet measured
The Results (page not supplied) report that ApoE increased Aβ oligomerization in vitro, with ApoE3 producing more oligomers than ApoE2; the carboxy-terminal fragment also enhanced oligomerization. The paper does not report an ApoE3ch condition, so it cannot support the claimed comparison between ApoE3ch and ApoE3 or ApoE2. (LLM, conf=0.88)
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.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“using a previously published split-luciferase complementation assay34”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Amyloid aggregation studies
What the sources say
- Could not verifycites [34] Hudry, E. et al. Sci. Transl. Med. 5, 12ra161 (2013). sourceExperimental — accuracy not yet measured
The Materials and Methods passages describe ELISA, immunoblotting, array tomography, and multiphoton imaging, but none describes a split-luciferase complementation assay. Searches for “split-luciferase complementation assay” and “luciferase protein complementation bioluminescence assay” found no passage addressing it. (LLM, conf=0.76)
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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a post hoc analysis of 117 kindred members,9 6% had one copy of this otherwise rare APOE3ch mutation (all closely related individuals), including four PSEN1 E280A mutation carriers who progressed to MCI at the mean age of 45.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Partly supportedcites [9] Lalli, M. A. et al. Mol. Psychiatry 20, 1294–1300 (2015). sourceExperimental — accuracy not yet measured
The Study populations and methods section (page unavailable) reports DNA from 117 kindred members and identifies 72 with PSEN1 E280A and reliable onset data. But the paper reports a chromosome 17 chemokine haplotype, not a post hoc APOE3ch analysis; our copy does not support the 6% frequency, four APOE3ch/PSEN1 carriers, or their mean MCI onset at 45. (LLM, conf=0.86)
plainn = 4- 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.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“based on the known toxicity of the oligomeric intermediates of Aβ35.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Amyloid aggregation studies
What the sources say
- Could not verifycites [35] Futamura, M. et al. J. Biol. Chem. 280, 5414–5422 (2005). sourceExperimental — accuracy not yet measured
The Experimental Procedures and SPR Measurements sections describe apoE binding to heparin, not a split-luciferase assay. Searches for Aβ oligomers, their toxicity, and split luciferase found no passage in our copy addressing the attributed claim; page numbers were unavailable. (LLM, conf=0.76)
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.
- Could not verify
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
“unusually high brain amyloid”
- Also stated in: § Abstract · plain
“She had unusually high positron emission tomography (PET) measurements of Aβ plaque burden, as indicated by a higher mean cortical-to-cerebellar Pittsburgh Compound B (PiB) distribution volume ratio (DVR=1.96) than in PSEN1 E280A carriers who developed MCI in their forties (DVRs 1.49–1.60).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plainSingle 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.
It may state two separate claims as one.
- Also stated in: § Abstract · plain
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
“limited tau/tangle and neurodegenerative measurements”
- Also stated in: § Abstract · plain
“Despite her high Aβ plaque burden, the magnitude and/or spatial extent of her PHF tau burden and neurodegeneration were relatively limited, particularly for her older age: Her flortaucipir (tau) PET measurements were restricted to medial temporal and occipital regions with relative sparing of other regions that are characteristically affected in the clinical stages of AD (Figure 1a).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plainSingle 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.
It may state two separate claims as one.
- Also stated in: § Abstract · plain
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
“Her memory deficits were limited to recent events and her neurological exams were normal.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plainSingle 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.
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
“The subject had a history of dyslipidemia treated with atorvastatin 40 mgs per day.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plainSingle case- 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 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
“While not previously diagnosed, the participant was confirmed to have HLP-III, including APOEch and elevated triglyceride and total cholesterol levels (Supplementary Table 4).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plainSingle case- 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.
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
“The subject’s fluorodeoxyglucose PET measurements of the cerebral metabolic rate for glucose (CMRgl, Figure 1b) were preserved in brain regions that are known to be preferentially affected by AD, including higher precuneus-to-whole brain glucose metabolism than PSEN1 E280A mutation carriers who developed MCI at younger ages.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
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.
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
“Genotyping of four descendants of the case were confirmed to be heterozygote carriers of the ApoE3ch as expected when one parent is homozygote (Extended data 2).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > APOE Genotyping by Sanger sequencing
plainSingle case- 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 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
“The per case estimated number of cells ranged from 2,495 to 3,716 for most cases, except for JA_98 (1,179 cells), the total number from all cases is 16,373 cells.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Single-cell RNA sequencing analysis
hedgedn = 6- 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.
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
“****p = 0.0000000042 for 55 μM Aβ42 vs. 55 μM Aβ42 + ApoE3WT”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Statistical analyses
plaindirectn = 2- 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 quote only partly states this claim.
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
“***p = 0.00022 for 55 μM Aβ42 vs. 55 μM Aβ42 + ApoE3ch”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Statistical analyses
plaindirectn = 2- 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.
The quote only partly states this claim.
In the paper
“the kindred’s carriers develop mild cognitive impairment (MCI) and dementia at the respective median ages of 44 (95% CI, 43–45) and 49 (95% CI, 49–50) years6.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Not checked — no full text of the sourcecites [6] Acosta-Baena, N. et al. Lancet Neurol. 10, 213–220 (2011). source
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.
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
“The mean reads per cell ranged from 43,470 to 82,240 (Supplementary Table 2).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Single-cell RNA sequencing analysis
plainn = 6- 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
“We postulate that APOE3ch exerts beneficial effects on downstream tau pathology and neurodegeneration, even in the face of high Aβ plaque burden, and that the beneficial effect is related, in part, to altered affinity for HSPG or other ApoE receptors.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
hedgedconditionalSingle 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.
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
“N = 3 columns per isoform in independent experiments.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > ELISA
plainSingle case- 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
“Genotypes of relatives of the R136S homozygote individual were determined by Sanger sequencing (Extended Data Figure 2).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Extended Data
plainSingle case- 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
“A monoclonal antibody was identified as capable of detecting both the wild type and Christchurch mutant ApoE3 (1343A).”
- Also stated in: § Antibody competition assay · plain
“The identify of the 1343A antibody was confirmed by RapidNovor (Canada) as fee-for-service.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Antibody competition assay
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- Also stated in: § Antibody competition assay · 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
“APOE3ch is the best candidate that we can clearly identify as a genetic modifier in this subject and fully recognize that other factors could have played a role to achieve such strong resistance phenotype.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
boostedconditionalSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Carriers of APOEch and other rare mutations in APOE’s low density lipoprotein receptor (LDLR) binding region commonly have hyperlipoproteinemia type III (HLP-III), similar to that observed in 5–10% of APOE2 homozygotes11.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Not checked — no full text of the sourcecites [11] Mahley, R. W., Huang, Y. & Rall, S. C. Jr. J. Lipid Res. 40, 1933–1949 (1999). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Cell concentration ranged from 7 – 12 × 105 cells/mL with 90–95% viability.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Single-cell RNA sequencing
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“All western blotting reported in Figure 2 are representative of two independent experiments.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Western blotting (WB)
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“We conducted n = 3 independent experiments.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Heparin-sepharose affinity chromatography
plainn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“Previous reports showed that compared to ApoE3, ApoE2 and ApoE3ch are associate with a 98% and 60% reductions in LDLR binding, respectively11,14.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Family links were verified by three family informants.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
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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
“We postulate that interventions that safely and sufficiently edit APOE, lower its expression, or modulate its pathogenic functions related to HSPG interactions could have a profound impact on the treatment and prevention of AD.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence.
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
“We used the 2-tailed unpaired T-test to analyze data obtained by the split-luciferase Assay (n = 2 independent experiments performed with n = 3 technical replicates; t = 2.758, DF = 1; p = 0.0202; Extended Data 3c).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Statistical analyses
plainn = 2- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Each cluster cell type was inferred by checking their marker genes expression profile against know gold standard single cell PBMC blood cell type labels in known PBMC dataset.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Single-cell RNA sequencing analysis
plain- Asserted: passes — The authors put it forward as true.
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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
“Institutional review boards from the University of Antioquia, Massachusetts General Hospital, and the Schepens Eye Research Institute of Massachusetts Eye and Ear approved this study. Like all of the research participants, the proband case provided her informed consent.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Clinical assessments
plainSingle case- Asserted: passes — The authors put it forward as true.
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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
“We used 2-way ANOVA followed by Tukey’s multiple comparisons test on n = 2 independent experiments (n = 3 technical replicates; F (2, 16) = 76.05; DF = 2; ****p = 0.00000797 for 55 μM Aβ42 + ApoE3WT vs. 55 μM Aβ42 + ApoE3ch; ****p = 0.0000000042 for 55 μM Aβ42 vs. 55 μM Aβ42 + ApoE3WT; ***p = 0.00022 for 55 μM Aβ42 vs. 55 μM Aβ42 + ApoE3ch) for the statistical analysis of the fibrillation assay (”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Statistical analyses
plainn = 2- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Our data support a model in which APOE variants differ in the extent of their pathogenic functions (APOE3ch and APOE2<3<4) and APOE3ch and APOE2 are associated with greatest functional loss.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“APOE, the major susceptibility gene for late-onset AD, has three common alleles (APOE2, 3, and 4).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Not checked — no full text of the sourcecites [10] Corder, E. H. et al. Nat. Genet. 7, 180–184 (1994). source
plain- 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.
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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
“The measurements were performed by board-certified laboratory technicians who were masked to clinical and genetic data.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Plasma NfL assay
plainSingle case- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Compared to the most common APOE3/3 genotype, which is considered neutral with regard to AD risk, APOE2 is associated with a lower AD risk and older age at dementia onset, and each additional copy of APOE4 is associated with a higher risk and younger age at onset.10”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
What the sources say
- Not checked — no full text of the sourcecites [10] Corder, E. H. et al. Nat. Genet. 7, 180–184 (1994). source
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.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Data representative of n=2 independent experiments and further validated independently with whole exome and whole genome sequencing.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
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
“For a quality control (QC) sample with a concentration 11.7 pg/mL, repeatability was 8.02% and intermediate precision was 20.2%. For a QC sample with a concentration 182 pg/mL, repeatability was 5.74% and intermediate precision was 8.34%.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Plasma NfL assay
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
AD-causing mutation carriers who remain cognitively unimpaired until older ages can help discover risk-reducing genes.
“Alzheimer’s disease (AD)-causing mutation carriers who remain cognitively unimpaired until older ages could help in the discovery of risk-reducing genes.”
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
“low Tau pathology in the ERC2.”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
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
“In vitro experiments from that report suggested that the APOE3ch variant may have protective effects by reducing ApoE binding to heparan sulfate proteoglycans and lipoprotein receptors involved in tau uptake and spread compared to other APOE variants.”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [1]
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
“possibly via different mechanisms including aggregation by modifying ApoE heparin binding [1], and homeostatic regulation of glial cells.”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [1]
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
“Recently, a study reported a homozygous APOE3 Christchurch mutation (R136S) carrier presenting a ~30-year delay in dementia onset caused by the PSEN1 E280A mutation and limited tau pathology despite abundant amyloid burden24.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [24]
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
“Similar to ApoE2, Christchurch (R136S) mutation is protective in autosomal dominant AD cases24,25 and AD mouse models26,27.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [24]
Experimental — accuracy not yet measured
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
“Consistent with the literature24, HPLC-based heparin binding assay performed on non-lipidated ApoE demonstrated impaired heparin binding by the Christchurch mutation on both ApoE3 and ApoE4 background with the overall ranking of ApoE4 > ApoE3 > ApoE4ch > ApoE2 > ApoE3ch > K146E ApoE4 (Figure S7A).”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [24]
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 rare ApoE R136S (Christchurch) variant, which is protective in the PSEN1 E280A kindred24,25.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [24]
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
“To date, few studies have reported on the effect of APOECh due to limited number of carriers in the population [5, 6, 8].”
From Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants (2023) · cites this paper as [5]
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 reported patient was protected from the clinical effects of PSEN1-E280A, a highly penetrant mutation causing EOAD dementia41,42, for 28 years by the homozygous APOE3-R136S mutation36.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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
“A recent discovery that a rare APOE variant, APOE3-R136S (APOE3-Christchurch)36, strongly protects against early-onset Alzheimer’s disease (EOAD)”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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
“This patient displayed extremely high Aβ pathology but minimal Tau burden, hippocampal atrophy and neuroinflammation36,43,44.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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
“A major functional effect of the R136S mutation is disruption of its binding to anionic HSPGs on cell surface36,45.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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 protection conferred by APOE3-R136S against EOAD caused by the PSEN1-E280A mutation is a milestone discovery36.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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
“that a single copy of the R136S mutation is not sufficient to overcome the detrimental effects of APOE4 on neuronal Tau pathology”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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
“by substituting a positively charged arginine residue for the uncharged serine, the affinity of the receptor-binding domain of APOE-R136S for negatively charged HSPGs is greatly diminished36,45,58”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
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
“It is important to note that HSPGs binding studies have shown that apoE4 had higher affinity than apoE3, apoE2 and apoE3 Christchurch, 29 and antibodies raised against the receptor‐binding region mimicked the protective effect of apoE2 and apoE3 Christchurch, 26”
From APOE and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [26]
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
“Taken together, and in light of the potential amyloid‐neutralizing effect of an apoE‐increasing mutation, 26 these ε2‐like and ε4‐like deviations of the structure of apoE have potential important biologic and therapeutic implications.”
From APOE and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [26]
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
“Of interest, this is highly supported by a novel report on the APOE Arg154Ser mutation (APOE3 Christchurch, old nomenclature Arg136Ser), where the effect of a dominant presenilin 1 mutation was neutralized in a woman from a large Columbian kindred with autosomal dominant AD. 26”
From APOE and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [26]
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
“In 2019, a case report [15] provided striking evidence that APOE is an essential mediator of plaque-induced tau pathology and subsequent neurodegeneration.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
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
“ApoeCh mice exhibited elevated plasma cholesterol (CHOL), mainly contributed by males (Fig. 1b) [15, 41].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
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
“HSPGs are responsible for neuronal uptake of tau and the R136S mutation causes impaired binding affinity of APOE to HSPGs, leading to reduced tau pathology [15, 41, 76, 84, 85].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
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
“ApoE3-Christchurch and ApoE3-Jacksonville have both been shown to be protective when compared with ApoE3 [35][36][37]”
From Utilizing a cell culture based novel cellular thermal shift assay to understand the isoform-dependent thermal stability of ApoE variants (2026) · cites this paper as [35]
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
“suggesting that mutations in the N-terminal receptor binding region likely act via mechanisms other than altered protein stability, such as heparan sulfate binding 35 .”
From Utilizing a cell culture based novel cellular thermal shift assay to understand the isoform-dependent thermal stability of ApoE variants (2026) · cites this paper as [35]
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
“Of interest also are the variants that did not impact stability in either variant namely ApoE3_R145C and ApoE3_Christchurch which indicate that these mutations are likely causing their effect due to other properties such as receptor or heparin binding 35 .”
From Utilizing a cell culture based novel cellular thermal shift assay to understand the isoform-dependent thermal stability of ApoE variants (2026) · cites this paper as [35]
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
“It has been shown that the protective effect of APOECh is partly due to its reduced affinity for heparan sulfate proteoglycans (HSPG) or other cellular receptors for APOE.21”
From Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer’s disease (2024) · cites this paper as [21]
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 discovery of the protective roles of Christchurch (R136S) in autosomal dominant PSEN1 familial AD and the Jacksonville (V236E), & R251G mutations that are protective against sporadic AD [17–20].”
From Discovery of a Missense Mutation (Q222K) of the APOE Gene from the Australian Imaging, Biomarker and Lifestyle Study (2023) · cites this paper as [17]
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 original case report further suggested that the PS1E280A individual would likely have exhibited a substantially greater amyloid burden in the absence of the protective APOE3ch genotype (Arboleda-Velasquez et al., 2019).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Arboleda-Velasquez et al., 2019
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 rare APOE3-R136S “Christchurch” variant (APOE3Ch) confers protection against AD.”
From APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells (2026) · cites this paper as Arboleda-Velasquez et al., 2019
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 discovery of the protective effects of APOE3Ch against AD (Arboleda-Velasquez et al., 2019) paved the way for mechanistic studies aimed at understanding protective APOE functions.”
From APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells (2026) · cites this paper as Arboleda-Velasquez et al., 2019
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
“In contrast, the protective Christchurch variant (APOE3*R136S) (21), the detrimental AD-risk increasing APOE3*R145C substitution when combined with APOE-ε4 (22) and a second recently discovered variant in APOE3*R189C (OR = 3.35, increased risk) (20), are all in the N-terminal domain.”
From APOE Isoform-Dependent Self-Association Measured by a Split-Luciferase Complementation Assay: Differential Effects of Disease-Risk and Protective Variants (2026) · cites this paper as [21]
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 protective effects of Christchurch have been attributed to reduced HSPG binding, which limits ApoE-mediated tau uptake and propagation, and to suppression of microglial cGAS-STING signaling (21,39,40).”
From APOE Isoform-Dependent Self-Association Measured by a Split-Luciferase Complementation Assay: Differential Effects of Disease-Risk and Protective Variants (2026) · cites this paper as [21]
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
“Mechanistic studies demonstrate that the APOE3Ch variant reduces binding to heparan sulfate proteoglycans (HSPGs), promoting cellular uptake and tau degradation and reducing tauopathy propagation. 5 , 6”
From Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [5]
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
“Homozygosity for APOE3Ch in this individual resulted in markedly reduced tau pathology and delayed dementia onset despite extensive amyloid deposition [3].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
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 observations could also reflect reduced cellular uptake and lysosomal degradation, consistent impaired receptor binding of APOE3Ch to its receptors such as LDLR and HSPGs [3, 16, 17]”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
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
“APOE3‐Ch has been associated with reduced Alzheimer's disease (AD) risk and neuroprotection in individuals carrying high‐risk genetic mutations for AD.”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [6]
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
“ApoE binding to heparan sulfate proteoglycans (HSPGs) has been suggested to promote Aβ aggregation and neuronal uptake of extracellular p‐tau [62]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection (2023) · cites this paper as [62]
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 protective effect of ApoE3ch is related to a lower affinity to bind HSPGs or other ligands [62]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection (2023) · cites this paper as [62]
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 Christchurch variant rs121918393 (APOEChc: CGC > aGC, p.Arg[R]136Ser[S]) [19–21] and the Jacksonville variant rs199768005 (APOEJax: GTG > GaG, p.Val[V]236Glu[E]) [22, 23] have been identified as protective variants against AD in Caucasians”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [20]
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
“For example, RMVs such as p.L46P (p.L28P; rs769452 [Pittsburgh]), 17 p.R154S (p.R136S; rs121918393 [Christchurch]), 18 p.R163C (p.R145C; rs769455), 19 p.V254E (p.V236E; rs199768005 [Jacksonville]), 20 and p.R269G (p.R251G; rs267606661) 21 have been reported in Western populations, suggesting potential resistance to amyloid-β (Aβ) accumulation, phosphorylated tau pathology, or the effects of the AP”
From Association of rare APOE missense variants with Alzheimer's disease in the Japanese population (2025) · cites this paper as [18]
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
“Interestingly, having an APOE2 allele (Berlau et al, 2007, 2009) or the rare isoform APOE3Ch (Christchurch variant) (Arboleda-Velasquez et al, 2019), shields patients against dementia even in the presence of high amyloid plaque load.”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Arboleda-Velasquez et al, 2019
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
“Recent case studies have identified variants in RELN and APOE as potentially mediating CR to autosomal-dominant AD.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [69]
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
“Notably, the RELN variant enhanced its binding to glycosaminoglycans (GAGs) and NRP1, and the APOE variant decreased binding to GAGs, potentially affecting their ability to compete for receptor binding69,70.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [69]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer’s disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden.”
From APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases (2024) · cites this paper as Arboleda-Velasquez et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“We previously reported a female carrying the PSEN1-E280A mutation with two copies of the APOE3 Christchurch (APOECh) (R136S) gene variant who remained cognitively unimpaired for nearly 30 years after the expected age at clinical onset2.”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“These imaging findings suggest that in this patient and in the APOECh homozygote case2, protection against ADAD dementia occurred even in the face of high amyloid burden (Fig. 1a,b).”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“because the encoded protein RELN modulates Tau phosphorylation4 and is functionally closely related to APOE, the gene mutated in the other case with extreme protection against ADAD2.”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“The APOECh mutation impairs APOE binding to GAG and the APOE receptors2,30.”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“We previously reported a female case homozygous for APOECh who was resistant to ADAD-related dementia”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“had widespread amyloid pathology”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“At the time of first examination, she was found to carry two copies of the rare APOE3 Christchurch variant (APOE3ch) and had severely elevated brain Aβ with limited tau pathology and neurodegeneration, as measured by in vivo PET imaging.”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer’s disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer’s symptoms for almost three decades beyond the expected age of onset.”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“who only developed cognitive impairment thirty years after the typical age of clinical onset for her kindred [1].”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“We previously reported the case of a person with the PSEN1E280A variant who also had two copies of the rare Christchurch variant (R136S) in APOE3 (APOE3Ch); in this person, mild cognitive impairment developed during her seventies — almost three decades after the expected age at onset.7”
From APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease (2024) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Our original report about one person in this population who was homozygous for APOE3Ch7 also discussed four persons with the PSEN1E280A variant who were heterozygous for APOE3Ch, and we did not describe a delay in the age at onset of cognitive impairment. This finding led us7 and others18 to initially conclude that APOE3Ch heterozygosity was not protective.”
From APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease (2024) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“In vivo and postmortem analyses showed that the APOE3Ch variant was linked to reduced tau accumulation and reduced neuroinflammation, which led to less neurodegeneration and less cerebral amyloid angiopathy within the context of higher cortical amyloid burden than is observed in persons with the PSEN1E280A variant and without the APOE3Ch variant.7,8”
From APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease (2024) · cites this paper as [7]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In vivo and postmortem analyses showed that the APOE3Ch variant was linked to reduced tau accumulation and reduced neuroinflammation, which led to less neurodegeneration and less cerebral amyloid angiopathy within the context of higher cortical amyloid burden than is observed in persons with the PSEN1E280A variant and without the APOE3Ch variant.7,8”
From APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease (2024) · cites this paper as [7]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“A recent case report implicated the APOE Christchurch variant (rs121918393) [5].That individual was also enrolled in this study, and while we do observe a nominally significant effect on age at onset of this variant, we note that the effect size is modest”
From Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred (2023) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“As previously noted, we and our colleagues recently found as association between two copies of the rare APOE3ch mutation and resistance to the clinical onset of AD in an Aβ42-overproducing PSEN1 E280A mutation carrier from the world’s largest ADAD kindred5.”
From Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study (2020) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“Interestingly, this individual had unusually high PET measurements of Aβ plaque burden, relatively limited PET measurements of PHF tau (neurofibrillary tangle) burden, minimal cerebral glucose hypometabolism in AD-affected brain regions, and like some APOE2 homozygotes, Type III hyperlipoproteinemia5,6.”
From Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study (2020) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“In one notable case, even harboring an autosomal dominant PSEN1 mutation was insufficient to cause overt dementia [36].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“However, rare cases of individuals who have one of these mutations and do not develop dementia symptoms until late life have recently been reported.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [105]
The cited source says what the claim attributes to it.
In the citing paper
“While the protective mechanism of the R136S variant has been attributed to reduced binding to heparan sulfate proteoglycans (HSPGs)24, it is unclear if it involves the lipidated state of ApoE.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“The protective effect of APOECh was observed for a single homozygous individual [5] but has been debated for heterozygous individuals [7].”
From Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants (2023) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“and are unable to validate the findings reported by Arboleda-Velasquez et al. [5]”
From Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants (2023) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“Notably, the APOE-R136S has severely reduced binding affinity to heparin, as the mutation occurs within the receptor-binding region of APOE36,45,58.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“The original patient showed AD protection with the homozygous APOE3-R136S mutation36.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“The original case report detailed protection of the APOE3-R136S mutation against autosomal-dominant AD, particularly in the face of extremely high Aβ burden36.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“HSPGs are suggested to play a role in neuronal uptake of tau and in amyloid beta metabolism, and apoE binding may play an important role here. 26 , 27”
From APOE and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [26]
The cited source says what the claim attributes to it.
In the citing paper
“Further investigation revealed she was homozygous for the rare Christchurch (R136S) variant in an APOE3 allelic background (encoding APOE3Ch), suggesting this might account for her cognitive preservation [15].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“The proband was heterozygous for the ADAD-associated PSEN1 E280A variant and was anticipated to develop AD by her forties although she remained cognitively intact until her seventies.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“This key study demonstrated that the presence of plaques can be separated from the development of AD.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Positron emission tomography (PET) imaging revealed significant Aβ plaque deposits in her brain, consistent with carriers of FAD mutations, but a relatively low and atypical burden of neurofibrillary tau tangles and neurodegeneration.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“The APOE3Ch variant offers a unique opportunity to explore the interplay between Aβ and tau, given its potential association with limited tau development and resistance to cognitive decline despite increased Aβ levels.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“The recent identification of an ADAD PSEN1-E280A carrier who was homozygous for the rare APOE Christchurch variant (R136S, APOECh) and who was resistant to the onset of ADAD dementia until her 70’s was a remarkable discovery [15].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies provide evidence that the Christchurch variant reduces AD pathology and associated CNS damage at least in part through alterations in receptor binding to LRP1, LDLR and/or HSPGs [15, 41, 76].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“E3 is the most common APOE variant and does not alter AD risk, while E4 elevates AD risk and E2 reduces AD risk12,13.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“The E3S/S patient had lower tau load compared to other individuals with the same PSEN1 mutation and high amyloid pathology12.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“In this study, we have demonstrated that the APOECh variant is causal to neuroprotection, extending the observation made in the 2019 single-patient study21 and providing strong rationale for developing potential AD therapies by targeting the protective APOECh variant and using the APOECh variant-carrying cells.”
From Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer’s disease (2024) · cites this paper as [21]
The cited source says what the claim attributes to it.
In the citing paper
“This includes the important discoveries about rare APOE missense variants that impact protein function and modify disease risk.”
From Discovery of a Missense Mutation (Q222K) of the APOE Gene from the Australian Imaging, Biomarker and Lifestyle Study (2023) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“The Christchurch variant R136S drew broad attention after a homozygous carrier in a PSEN1 E280A kindred showed a striking delay in age-at-onset of symptoms 6”
From Association of Rare APOE Missense Variants R189C and W276C With Risk of Alzheimer Disease (2026) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Recently, a rare variant, APOE3 Christchurch (APOE3ch), was identified in an individual who was heterozygous for the pathogenic PSEN1 E280A mutation and homozygous for APOE3ch and who exhibited a markedly delayed onset of disease (Arboleda-Velasquez et al., 2019).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Arboleda-Velasquez et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“Regarding the APOE3ch variant, early in vitro studies indicated that APOE3ch reduces Aβ42 aggregation compared with wild-type APOE3 (Arboleda-Velasquez et al., 2019).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Arboleda-Velasquez et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“This suggests that APOE3ch may confer resilience against AD pathology, though the mechanisms underlying its protective effects remain poorly understood.”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Arboleda-Velasquez et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“Early findings indicate that APOE3ch may disrupt interactions with heparan sulfate proteoglycans (HSPGs), which influence amyloid aggregation and tau pathology (Arboleda-Velasquez et al., 2019).”
From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Arboleda-Velasquez et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“The R136S (Christchurch) mutation has been reported to confer protection against AD on the basis of a unique individual carrying the PSEN1 E280A mutation who was homozygous for the APOEε3 allele with the R136S mutation36.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“The protective effect of the APOE R136S mutation seems to require homozygosis, given that four individuals with PSEN1-E280A and heterozygous for APOEε3R136S developed mild cognitive impairment at the expected age of 45 years36 and some APOEε3R136S heterozygous individuals with autopsy-proven AD had early onset of symptoms40.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“Initial in vitro functional experiments with the APOE Christchurch protective mutation (see the section ‘R136C (Christchurch)’) suggest that this mutation weakens the interaction between APOE and heparan sulfate proteoglycans — located on the surface of neurons and implicated in tau uptake — and, therefore, that blocking APOE–heparan sulfate proteoglycan binding might have therapeutic value36”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [36]
The cited source says what the claim attributes to it.
In the citing paper
“Within this cohort, a remarkable case of resistance to ADAD was identified: a woman homozygous for the rare apolipoprotein E (APOE3) Christchurch (APOE3Ch ) variant (R136S) who remained cognitively unimpaired until her seventies, despite carrying the PSEN1E280A mutation. 5”
From Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“APOE3Ch carriers are known to have hyperlipoproteinemia 5 though it is unknown whether they have differences in the EVs properties and functional roles.”
From Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“This would align with previous in vitro studies reporting decreased Aβ aggregation in the presence of recombinant APOE3Ch compared with APOE3 [3, 24].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Mounting evidence from human-based, in vitro, and in vivo studies has linked APOE3Ch to reduction in tau pathology [3–7, 24, 26, 41, 42].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting the distinct biochemical interactions influencing Aβ deposition or clearance [2, 3, 22, 23].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“homozygosity for this rare APOE3 variant was found to be resilient against the onset of a very aggressive form of autosomal AD case driven by the PSEN1 p.E280A mutation, despite extensive amyloid deposition [3].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“clinical observations in the original APOE3Ch homozygote carrier, who exhibited limited neurodegeneration despite high Aβ load [3].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Based on patient studies showing limited tau pathology in the individual carrying the APOE3‐Ch variant and the familial AD mutation PSEN1‐E280A, 6 we hypothesized that the APOE3‐Ch variant enhances astrocytic tau clearance and thereby limits tau spread in the brain.”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Fascinatingly, our group identified an E280A carrier who did not develop FAD and instead displayed mild cognitive impairment three decades after the expected age of clinical onset [62]. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch), which has been recognized as its most likely genetic modifier.”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection (2023) · cites this paper as [62]
The cited source says what the claim attributes to it.
In the citing paper
“Individuals carrying the PSEN1 p.E280A mutation typically develop mild cognitive impairment at a median age of 44 years (95% confidence interval [CI]: 43‒45 years) and dementia at a median age of 49 years (95% CI: 49‒50 years).”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“Surprisingly, a woman with homozygous APOEChc variant and carrying the PSEN1 p.E280A mutation did not exhibit mild cognitive impairment until her 70 s even though abundant accumulation of amyloid-β (Aβ) was seen in the brain.”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“with the APOEChc variant apparently reducing the effects of the pathogenic PSEN1 variant (GAA > GcA, p.Glu[E]280Ala[A]), which is a highly penetrant and causative mutation for dominantly inherited AD [20, 21]”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“The Christchurch mutation (R136S) on the APOE3 (E3S/S) gene is associated with attenuation of tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high levels of amyloid beta pathology in the carrier1.”
From APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“an APOE3 Christchurch (R136S) homozygote carrying a causal AD mutation (E280A) in the presenilin1 (PSEN1) gene displays minimal tau pathology and neurodegeneration and is resistant to autosomal dominant AD”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Arboleda-Velasquez et al 2019
The cited source says what the claim attributes to it.
In the citing paper
“Notably, a homozygous carrier of the APOE Christchurch mutation was reported to be resistant to cognitive decline and pTau accumulation, even in the presence of a presenilin 1 mutation and robust amyloid plaque deposition (67).”
From Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol (2021) · cites this paper as [67]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Despite broader age variability, evidence supports a protective role for APOE3Ch : homozygous carriers showed reversal of cerebral hypometabolism, 5 and heterozygotes exhibited reduced angiogenesis and cerebral amyloid angiopathy. 3”
From Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [5]
Experimental — accuracy not yet measuredIn the citing paper
“She was also found to be homozygous for the Apolipoprotein E3 Christchurch (APOE3Ch) variant (R136S), which was identified as a candidate variant responsible for her resistance to ADAD (Arboleda-Velasquez et al., 2019).”
From APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases (2024) · cites this paper as Arboleda-Velasquez et al., 2019
In the citing paper
“The ApoE3Ch variant was found in a protected ADAD subject and was shown to have weaker binding than its ApoE3 WT counterpart to heparin sulfate proteoglycans (Arboleda-Velasquez et al., 2019).”
From APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases (2024) · cites this paper as Arboleda-Velasquez et al., 2019
In the citing paper
“The value of this family for the nomination of genetic variants that delay the onset of AD was recently affirmed by the report of a PSEN1 E280A carrier who developed MCI nearly three decades after the kindred's median age at clinical onset [5]”
From Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred (2023) · cites this paper as [5]
In the citing paper
“Its tendency to accumulate for years without causing symptomatic disease (i.e., asymptomatic AD or AsymAD) supports this conclusion [35, 36].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [36]
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
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Abstract
“Her MRI-based hippocampal-to-whole brain volume, an atrophy measurement that can be affected by AD and/or normal aging, was within the range of mutation carriers who developed MCI in their forties (Figure 1c).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > MRI and PET imaging
“Hippocampal to total intracranial volume ratios were characterized from bilateral ROIs in each participant’s T1-weighted MR image using FreeSurfer (http://surfer.nmr.mgh.harvard.edu).”
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
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Statistical analyses
“split-luciferase Assay (n = 2 independent experiments performed with n = 3 technical replicates; t = 2.758, DF = 1; p = 0.0202; Extended Data 3c).”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Extended Data
“Representative data presented as individual values ± SEM of n=3 independent experiments.”
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
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Statistical analyses
“t = 2.758, DF = 1; p = 0.0202; Extended Data 3c”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Extended Data
“(*p = 0.0202, 2-tailed unpaired T-test, n=6).”
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
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Single-cell RNA sequencing
“generating over 40M reads per cell.”
§ Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report > Methods > Single-cell RNA sequencing analysis
“The mean reads per cell ranged from 43,470 to 82,240 (Supplementary Table 2).”
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“264”
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“The study concluded that the APOE3ch homozygote conferred resistance to the clinical onset of AD by limiting tau pathology even in the face of high amyloid-β plaque burden (74).”
BackgroundMolecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases
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“Both the Christchurch mutation in APOE 149 and a mutation in reelin ( RELN ) conferred resilience to an autosomal dominant AD mutation in PSEN1 (ref.”
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“edit APOE comes from the recent report that homozygosis for the APOE3 Christchurch variant (R136S) markedly delayed cognitive decline in a single presenilin 1 (PSEN1) mutation carrier [146].”
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Predicting Symptom Onset in Sporadic Alzheimer Disease With Amyloid PET
Schindler, S. E., Li, Y., Buckles, V. D., Gordon, B. A., Benzinger, T. L. S., Wang, G., Coble, D., Klunk, W. E., Fagan, A. M., Holtzman, D. M., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000012775 · Cited by 89
“Brain amyloid deposition is necessary but not sufficient for symptomatic AD, and many other genetic, biological, and social factors are likely involved in expression of symptoms.(41,42) Analyses of larger numbers of progressors will likely improve modeling of factors that are known to modify the risk of symptomatic AD…”
The Amyloid Cascade Hypothesis in Alzheimer’s Disease: Should We Change Our Thinking?
Kurkinen, M. T., Fułek, M., Fułek, K., Beszłej, J. A., Kurpas, D., & Leszek, J. (2023) · Biomolecules · doi:10.3390/biom13030453 · Cited by 105
Kalaria, R. N., Maestre, G. E., Mahinrad, S., Acosta, D. M., Akinyemi, R., Alladi, S., Allegri, R., Arshad, F., Babalola, D. O., Baiyewu, O., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13836 · Cited by 110
“158 Brain imaging and autopsy revealed low levels of tau pathology and neurodegeneration in key cortical areas, despite a high A β plaqueburden.”
Self-citationSepulveda-Falla, D., Sanchez, J. S., Almeida, M. C., Boassa, D., Acosta-Uribe, J., Vila-Castelar, C., Ramirez-Gomez, L., Baena, A., Aguillon, D., Villalba-Moreno, N. D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02467-8 · Cited by 92
“The strong putative protective effect of homozygous APOE3ch in this patient suggests that ApoE may be one of the main modulators of tau pathology in AD, possibly via different mechanisms including aggregation by modifying ApoE heparin binding [1], and homeostatic regulation of glial cells.”
BackgroundMethodResultInfluentialSelf-citationStep by step: towards a better understanding of the genetic architecture of Alzheimer’s disease
Lambert, J.-C., Ramirez, A., Grenier-Boley, B., & Bellenguez, C. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02076-1 · Cited by 87
“Lastly, two copies of the APOE3 R136S mutation were suggested to have delayed the development of AD by several decades in an individual carrying a PSEN1 mutation [64].”
BackgroundLipoproteins in the Central Nervous System: From Biology to Pathobiology
Raulin, A.-C., Martens, Y. A., & Bu, G. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104801 · Cited by 89
Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease
Le Guen, Y., Belloy, M. E., Grenier-Boley, B., de Rojas, I., Castillo-Morales, A., Jansen, I., Nicolas, A., Bellenguez, C., Dalmasso, C., Küçükali, F., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.1166 · Cited by 93
Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91
“24 A mildly protective effect of the heterozygous Christchurch mutation was also found in the same kindred.”
InfluentialAlzheimer’s disease – the journey of a healthy brain into organ failure
Golde, T. E. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00523-1 · Cited by 98
Gamache, J., Yun, Y., & Chiba-Falek, O. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.045211 · Cited by 84
Mifflin, M. A., Winslow, W., Surendra, L., Tallino, S., Vural, A. S., & Velázquez, R. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.01.018 · Cited by 84
Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework
Mentis, A. A., Dardiotis, E., & Chrousos, G. P. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0731-7 · Cited by 83
“Interestingly, the role of APOE in the CNS is further illustrated by a recently described ultrarare mutation in the APOE3 gene, which confers resistance to developing familial autosomal-dominant AD [29].”
BackgroundSnow, A. D., Cummings, J. A., & Lake, T. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.710683 · Cited by 84
Current directions in tau research: Highlights from Tau 2020
Sexton, C. E., Snyder, H. M., Beher, D., Boxer, A. L., Brannelly, P., Brion, J., Buée, L., Cacace, A. M., Chételat, G., Citron, M., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12452 · Cited by 89
Self-citationLewandowski, C. T., Maldonado Weng, J., & LaDu, M. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104811 · Cited by 72
Remembering your A, B, C's: Alzheimer's disease and ABCA1
Lewandowski, C. T., Laham, M. S., & Thatcher, G. R. J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.01.011 · Cited by 76
Lipid metabolism, remodelling and intercellular transfer in the CNS
Vanherle, S., Loix, M., Miron, V. E., Hendriks, J. J. A., & Bogie, J. F. J. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00908-3 · Cited by 96
Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
Belaidi, A. A., Bush, A. I., & Ayton, S. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00843-y · Cited by 91
“…APOE ε3 Christchurch allele was discovered in a Colombian woman carrying the PSEN1 E280A mutation, who instead of developing cognitive impairment at 44 years of age, presented with mild cognitive impairment in her late 70s and thus was protected from developing dementia for nearly 3 decades [32].”
InfluentialPersistent repression of tau in the brain using engineered zinc finger protein transcription factors
Wegmann, S., DeVos, S. L., Zeitler, B., Marlen, K., Bennett, R. E., Perez-Rando, M., MacKenzie, D., Yu, Q., Commins, C., Bannon, R. N., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe1611 · Cited by 77
Self-citationAstrocyte-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
Association of APOE Genotype With Heterogeneity of Cognitive Decline Rate in Alzheimer Disease
Qian, J., Betensky, R. A., Hyman, B. T., & Serrano-Pozo, A. (2021) · Neurology · doi:10.1212/wnl.0000000000011883 · Cited by 71
Lodder, C., Scheyltjens, I., Stancu, I., Lucena, P. B., de Ravé, M. G., Vanherle, S., Vanmierlo, T., Cremers, N., Vanrusselt, H., Brône, B., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01204-8 · Cited by 71
“An APOE3 Christchurch (R136S) mutation carrier did not develop strong tau pathology and neurodegeneration and remained symptom free until late age [1].”
(ADNI), A. D. N. I., Kleineidam, L., Chouraki, V., Próchnicki, T., van der Lee, S. J., Madrid-Márquez, L., Wagner-Thelen, H., Karaca, I., Weinhold, L., Wolfsgruber, S., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02138-6 · Cited by 62
“In addition, in 2019, a rare protective coding variant in APOE, different from the APOE-ε2 allele, was found to mitigate downstream effects of amyloid-beta formation [3], as observed for p.”
BackgroundCiccone, L., Shi, C., di Lorenzo, D., Van Baelen, A.-C., & Tonali, N. (2020) · Molecules · doi:10.3390/molecules25102439 · Cited by 69
“More recently, it has been shown that a homozygous APOE3ch mutation can impart resistant to the clinical onset of AD pathogenesis, probably having beneficial effects on downstream tau pathology and neurodegeneration, even in the face of high Aβ plaque burden [18].”
BackgroundMinta, K., Brinkmalm, G., Janelidze, S., Sjödin, S., Portelius, E., Stomrud, E., Zetterberg, H., Blennow, K., Hansson, O., & Andréasson, U. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00585-7 · Cited by 57
Self-citationThe shared role of cholesterol in neuronal and peripheral inflammation
Hansen, S. B., & Wang, H. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108486 · Cited by 69
Translational approaches to understanding resilience to Alzheimer’s disease
Neuner, S. M., Telpoukhovskaia, M., Menon, V., O’Connell, K. M. S., Hohman, T. J., & Kaczorowski, C. C. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.02.005 · Cited by 68
“This specific incidence of resilience was attributed to the presence of a homozygous APOE variant known as the Christchurch mutation [23] that confers reductions in low-density lipoprotein receptor and heparin binding [20], implicating these mechanisms as putative drivers of resilience in the face of high amyloid depo…”
BackgroundInfluentialThe MAPT H1 Haplotype Is a Risk Factor for Alzheimer’s Disease in APOE ε4 Non-carriers
Sánchez‐Juan, P., Moreno–Grau, S., de Rojas, I., Hernández, I., Valero, S., Alegret, M., Montrreal, L., García‐González, P., Lage, C., López‐García, S., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00327 · Cited by 61
Apolipoprotein E in Alzheimer’s disease trajectories and the next-generation clinical care pathway
Narasimhan, S., Holtzman, D. M., Apostolova, L. G., Cruchaga, C., Masters, C. L., Hardy, J., Villemagne, V. L., Bell, J. S., Cho, M., & Hampel, H. J. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01669-5 · Cited by 70
“…explanation, a previous study showed that the APOE3 Christchurch mutation in a homozygous state was associ ated with a 30year delay in cognitive decline in one individual carrier with the PSEN1(E280A) mutation 29 , with evidence of Aβ deposition but attenuated tau pathology and inflammation 30 .”
Cognitive Impairment in Older Adults and Therapeutic Strategies
Montine, T. J., Bukhari, S. A., & White, L. R. (2020) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000031 · Cited by 67
“Another example of a resistance factor is theAPOEChristchurch mutation; homozygosity for this rare variant conferred apparent resistance to a person with a disease-causing presenilin 1mutation (Arboleda-Velasquez et al., 2019).”
BackgroundAPOE and dementia – resequencing and genotyping in 105,597 individuals
Rasmussen, K. L., Tybjærg‐Hansen, A., Nordestgaard, B. G., & Frikke‐Schmidt, R. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12165 · Cited by 64
Genetics of Alzheimer’s disease: An East Asian perspective
Miyashita, A., Kikuchi, M., Hara, N., & Ikeuchi, T. (2023) · Journal of Human Genetics · doi:10.1038/s10038-022-01050-z · Cited by 64
“Glu[E]280Ala[A]), which is a highly penetrant and causative mutation for dominantly inherited AD [20, 21].”
BackgroundGenetic testing for neurodegenerative diseases: Ethical and health communication challenges
Roberts, J. S., Patterson, A. K., & Uhlmann, W. R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104871 · Cited by 71
APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease
Quiroz, Y. T., Aguillon, D., Aguirre-Acevedo, D. C., Vasquez, D., Zuluaga, Y., Baena, A. Y., Madrigal, L., Hincapié, L., Sanchez, J. S., Langella, S., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2308583 · Cited by 63
Self-citationSanchez, J. S., Hanseeuw, B. J., Lopera, F., Sperling, R. A., Baena, A., Bocanegra, Y., Aguillon, D., Guzmán-Vélez, E., Pardilla-Delgado, E., Ramirez-Gomez, L., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00765-5 · Cited by 58
“This is consistent with a recent report of a PSEN1 E280A carrier who also carried the APOE3 Christchurch mutation and, remarkably, was in her seventies with severely elevated neocortical Aβ, but relatively limited neocortical tau and preserved cognitive function [46].”
Self-citation
Metadata
- Authors
- Arboleda-Velasquez, J. F., Lopera, F., O’Hare, M., Delgado-Tirado, S., Marino, C., Chmielewska, N., Saez-Torres, K. L., Amarnani, D., Schultz, A. P., Sperling, R. A., Leyton-Cifuentes, D., Chen, K., Baena, A., Aguillon, D., Rios-Romenets, S., Giraldo, M., Guzmán-Vélez, E., Norton, D. J., Pardilla-Delgado, E., Artola, A., Sanchez, J. S., Acosta-Uribe, J., Lalli, M., Kosik, K. S., Huentelman, M. J., Zetterberg, H., Blennow, K., Reiman, R. A., Luo, J., Chen, Y., Thiyyagura, P., Su, Y., Jun, G. R., Naymik, M., Gai, X., Bootwalla, M., Ji, J., Shen, L., Miller, J. B., Kim, L. A., Tariot, P. N., Johnson, K. A., Reiman, E. M., & Quiroz, Y. T.
- Affiliations
- Universidad de Antioquia (CO)
- Massachusetts Eye and Ear Infirmary (US)
- Boston College (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- University of Arizona (US)
- University of California, Santa Barbara (US)
- Translational Genomics Research Institute (US)
- Sahlgrenska University Hospital (SE)
- Banner Alzheimer’s Institute (US)
- Boston University (US)
- University of Southern California (US)
- Children's Hospital Los Angeles (US)
- Corresponding author
- Reiman, Eric M.
- Quiroz, Yakeel T.
- ORCID
- Arboleda-Velasquez, Joseph F.
- Lopera, Francisco
- O’Hare, Michael
- Chmielewska, Natalia
- Amarnani, Dhanesh
- Schultz, Aaron P.
- Sperling, Reisa A.
- Leyton-Cifuentes, David
- Chen, Kewei
- Baena, Ana
- Aguillon, David
- Giraldo, Margarita
- Norton, Daniel J.
- Pardilla-Delgado, Enmanuelle
- Artola, Arabiye
- Sanchez, Justin S.
- Lalli, Matthew
- Kosik, Kenneth S.
- Huentelman, Matthew J.
- Zetterberg, Henrik
- Blennow, Kaj
- Luo, Ji
- Chen, Yinghua
- Thiyyagura, Pradeep
- Su, Yi
- Jun, Gyungah R.
- Naymik, Marcus
- Gai, Xiaowu
- Bootwalla, Moiz
- Ji, Jianling
- Shen, Lishuang
- Miller, John B.
- Kim, Leo A.
- Tariot, Pierre N.
- Johnson, Keith A.
- Reiman, Eric M.
- Quiroz, Yakeel T.
- Venue
- Nature Medicine
- Published
- 2019-11
- Volume
- 25
- Issue
- 11
- Pages
- 1680-1683
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6898984
- OpenAlex
- W2989361381
- Cited by
- 598
- References
- 38
- Citations by year
- 2026: 73 · 2025: 100 · 2024: 111 · 2023: 80 · 2022: 74 · 2021: 69 · 2020: 82 · 2019: 7
- FWCI
- 39.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Institutional Repository University of Antioquia (University of Antioquia) (acceptedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (DP5OD019833)
- National Institute on Aging (R01AG055444, R01AG031581, P30AG019610, R01AG054671, RF1AG057519, P30AG062421)
- National Institute of Neurological Disorders and Stroke (RF1NS110048, RM1NS132996, UH3NS100121)
- 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
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- autosomal dominant Alzheimer's disease, mild cognitive impairment, brain amyloid, amyloid plaques, tau pathology, neurodegeneration
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Brain, Female, Homozygote, Humans, Male, Mutation, Pedigree, Neurodegenerative Diseases, Apolipoprotein E3, Apolipoprotein E2, Presenilin-1, Cognitive Dysfunction
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