APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease
Open accessAbstract
Background Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer’s disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer’s disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant ( APOE3 Ch ). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. Methods We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. Results Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18 F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer’s disease. In one of these participants, who underwent 18 F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. Conclusions Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer’s disease. (Funded by Good Ventures and others.)
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Claims the paper makes
14 of 19 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured
- Study design and conductcitation
The neuropsychological battery had been adapted and validated to detect Alzheimer's disease-related cognitive impairment in this kindred.
“Neuropsychological assessments were conducted in Spanish with the use of a battery that has been adapted and validated for the detection of Alzheimer’s disease–related cognitive impairment in this kindred”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [10] Aguirre-Acevedo DC, Lopera F, Henao E, Cognitive decline in a Colombian kindred with autosomal dominant Alzheimer disease: a retrospective cohort study. JAMA Neurol 2016; 73: 431– 8. 26902171 PMC5505685 source
Methods > Procedures (page unavailable) says the CERAD battery and MMSE were validated in the study population, and the Discussion says CERAD is sensitive to early changes associated with mild cognitive impairment. The copy does not state that the battery was adapted or specifically validated to detect Alzheimer’s-related impairment in this kindred. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [11] Aguirre-Acevedo DC, Jaimes-Barragán F, Henao E, Diagnostic accuracy of CERAD total score in a Colombian cohort with mild cognitive impairment and Alzheimer’s disease affected by E280A mutation on presenilin-1 gene. Int Psychogeriatr 2016; 28: 503– 10. 26478578 source
- cites [12] Torres VL, Vila-Castelar C, Bocanegra Y, Normative data stratified by age and education for a Spanish neuropsychological test battery: results from the Colombian Alzheimer’s prevention initiative registry. Appl Neuropsychol Adult 2021; 28: 230– 44. 31230490 PMC6926163 source
- Study design and conductcitation
The intervals between tests were homogeneous for APOE3Ch carriers and noncarriers.
“The intervals between testing have been analyzed previously and were homogeneous across APOE3Ch carriers and noncarriers.1,10”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [1] Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol 2011; 10: 213– 20. 21296022 source
- cites [10] Aguirre-Acevedo DC, Lopera F, Henao E, Cognitive decline in a Colombian kindred with autosomal dominant Alzheimer disease: a retrospective cohort study. JAMA Neurol 2016; 73: 431– 8. 26902171 PMC5505685 source
The Discussion reports a median of 2 years between assessments for participants with repeated testing, but does not compare testing intervals by APOE3Ch status. The Genetic Analyses and Exploratory Analysis sections examine APOE ε4, not APOE3Ch. Searches for homogeneous testing intervals and APOE3Ch carriers found no passage addressing the claimed comparison. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
A previously reported person with PSEN1E280A and two APOE3Ch copies developed mild cognitive impairment in her seventies, nearly thirty years later than expected.
“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”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [7] Arboleda-Velasquez JF, Lopera F, O’Hare M, Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med 2019; 25: 1680– 3. 31686034 PMC6898984 source
- Findingown data
The four APOE3Ch heterozygous autopsy cases had more amyloid-β plaque than PSEN1E280A carriers with typical-age mild cognitive impairment, judged qualitatively and not quantified.
“The four participants who were heterozygous for APOE3Ch and had available autopsy material had a greater amyloid-β plaque burden and a relatively limited tau burden as compared with PSEN1E280A variant carriers in whom mild cognitive impairment had occurred at the kindred’s typical age as determined by qualitative visual inspection, but this observation was not quantified.”
Quote in the paperSubstantial claim - Findingown data
Among APOE3Ch heterozygous carriers, the median age when dementia began was 54 years, with a 95% confidence interval of 49 to 57.
“The median age at the onset of dementia among APOE3Ch carriers was 54 years (95% CI, 49 to 57), which indicated an apparent delay as compared with the noncarriers, among whom the median age at onset was 50 years (95% CI, 48 to 51) (Table S3).”
Quote in the paperSubstantial claim
- Findingown data
Autopsy tissue from four people carrying both APOE3Ch and PSEN1E280A had fewer vascular amyloid abnormalities than tissue from PSEN1E280A carriers lacking APOE3Ch.
“Four studies of autopsy material obtained from persons with the APOE3Ch and PSEN1E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1E280A variant but not the APOE3Ch variant.”
Quote in the paperSubstantial claim - Findingown data
Vessels from APOE3Ch heterozygous or homozygous participants were more similar to controls in length, branching pattern, and spacing than vessels from PSEN1E280A carriers without APOE3Ch.
“Furthermore, vessels that were analyzed in participants who were heterozygous or homozygous for APOE3Ch showed greater similarity to controls in terms of length, branching pattern, and spacing between them than those obtained from PSEN1E280A carriers without the APOE3Ch variant (Fig. S8).”
Quote in the paperSubstantial claim - Findingown data
Among PSEN1E280A carriers heterozygous for APOE3Ch, the median age when mild cognitive impairment began was 52 years, with a 95% confidence interval of 51 to 58.
“Survival analyses of the matched samples showed that the median age at the onset of mild cognitive impairment was 52 years (95% CI, 51 to 58) among APOE3Ch carriers, as compared with approximately 47 years (95% CI, 47 to 49) in the matched sample of noncarriers.”
Quote in the paperSubstantial claim - Findingown data
The brains of APOE3Ch heterozygous carriers in the current study did not show the tau deposition pattern seen in the APOE3Ch homozygous case.
“In contrast, the brains of the APOE3Ch heterozygous carriers in the current study did not show this pattern of tau deposition.”
Quote in the paperSubstantial claim - Findingown data
Among noncarriers, the median age when dementia began was 50 years, with a 95% confidence interval of 48 to 51.
“The median age at the onset of dementia among APOE3Ch carriers was 54 years (95% CI, 49 to 57), which indicated an apparent delay as compared with the noncarriers, among whom the median age at onset was 50 years (95% CI, 48 to 51) (Table S3).”
Quote in the paperSubstantial claim - Findingown data
APOE3Ch carriers had a numerically lower percentage of partial vessel wall involvement than noncarriers in frontal and occipital cortex cerebral amyloid angiopathy.
“In addition, APOE3Ch carriers had a numerically lower percentage of partial involvement of vessel walls (present only in a portion the annular circumferences of walls) than noncarriers, with pathological findings of cerebral amyloid angiopathy in frontal and occipital cortexes (Figs. S7B and S7C).”
Quote in the paperNot a substantial claim - Findingown data
In two participants with both APOE3Ch and PSEN1E280A variants who had brain imaging, FDG PET showed metabolism that was relatively preserved in regions usually affected by Alzheimer's disease.
“In two participants with the APOE3Ch and PSEN1E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer’s disease.”
Quote in the paperSubstantial claim - Findingown data
Among matched PSEN1E280A carriers without APOE3Ch, the median age when mild cognitive impairment began was about 47 years, with a 95% confidence interval of 47 to 49.
“Survival analyses of the matched samples showed that the median age at the onset of mild cognitive impairment was 52 years (95% CI, 51 to 58) among APOE3Ch carriers, as compared with approximately 47 years (95% CI, 47 to 49) in the matched sample of noncarriers.”
Quote in the paperSubstantial claim - Findingown data
The four APOE3Ch heterozygous autopsy cases had relatively limited tau burden compared with PSEN1E280A carriers with typical-age mild cognitive impairment, judged qualitatively and not quantified.
“The four participants who were heterozygous for APOE3Ch and had available autopsy material had a greater amyloid-β plaque burden and a relatively limited tau burden as compared with PSEN1E280A variant carriers in whom mild cognitive impairment had occurred at the kindred’s typical age as determined by qualitative visual inspection, but this observation was not quantified.”
Quote in the paperSubstantial claim - Findingown data
In one such participant who had 18F-flortaucipir PET, tau deposition was limited relative to PSEN1E280A carriers who developed cognitive impairment at the usual age for this kindred.
“In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1E280A in whom cognitive impairment occurred at the typical age in this kindred.”
Quote in the paperNot a substantial claim - Findingown data
Cerebral amyloid angiopathy pathology was less prominent in the frontal cortex of APOE3Ch carriers than in noncarriers.
“Pathological findings of cerebral amyloid angiopathy were less prominent in the frontal cortex in APOE3Ch carriers (Fig. S7A) than in noncarriers.”
Quote in the paperSubstantial claim - Interpretationown data
Clinical data supported later cognitive impairment onset among APOE3Ch heterozygotes in this kindred with high prevalence of autosomal dominant Alzheimer's disease.
“Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer’s disease.”
- Also stated in: § DISCUSSION · hedged
“The clinical, cognitive, neuroimaging, and neuropathological data that we present here provide evidence that APOE3Ch heterozygosity delayed the onset of cognitive impairment in a form of autosomal dominant Alzheimer’s disease and may have a protective effect against Alzheimer’s disease and neurodegeneration in this population.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Study design and conductown data
The analysis matched carriers and noncarriers of APOE3Ch on sex, APOE genotype, and formal education to control confounding.
“To control for potential confounding factors of sex, APOE genotype, and years of formal education, we established a matched sample between carriers and noncarriers of the APOE3Ch variant.”
Quote in the paperSubstantial claim- Rests on an assumption: The comparison between APOE3Ch carriers and noncarriers is not confounded by unmeasured factors.
- Study design and conductown data
The precision of the estimates was probably unaffected by irregular testing intervals because intervals were homogeneous across the entire PSEN1E280A group.
“The precision of these estimates was probably not affected by irregular intervals between testing for the reasons noted above, including homogeneity of intervals across the entire group of persons with the PSEN1E280A variant.”
Quote in the paperSubstantial claim - Interpretationown data
The delay in clinical onset among APOE3Ch heterozygotes was smaller than that observed in the previously reported APOE3Ch homozygote.
“The apparent delay in the onset of clinical features that were attributable to autosomal dominant Alzheimer’s disease in participants who were heterozygous for the APOE3Ch variant was less than that observed in a previously reported case of APOE3Ch homozygosity.”
Quote in the paperNot a substantial claim - Study design and conductown data
Testing gaps of up to 5 years may have made the ages when mild cognitive impairment and dementia began imprecise in both groups.
“Some imprecision in the ages at the onset of mild cognitive impairment and dementia in both groups may have been introduced by gaps in testing that could have been as long as 5 years.”
Quote in the paperNot a substantial claim - Premisecitation
It is nearly certain that PSEN1E280A carriers will develop autosomal dominant Alzheimer's disease.
“Autosomal dominant Alzheimer’s disease is destined, with near 100% certainty, to develop in these carriers of PSEN1E280A.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol 2011; 10: 213– 20. 21296022 source
- Study design and conductcitation
The small number of people carrying both APOE3Ch and PSEN1E280A, plus the homogeneity of this genetic isolate, increase uncertainty around the differences in onset ages.
“Limitations of this study arise from the relatively small number of persons who have both the APOE3Ch and PSEN1E280A variants, as well as the homogeneity of the population belonging to a genetic isolate.19 These limitations increase uncertainty around differences in the point estimates for the ages at the onset of mild cognitive impairment and dementia.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Bedoya G, Montoya P, García J, Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate. Proc Natl Acad Sci U S A 2006; 103: 7234– 9. 16648268 PMC1464326 source
- May combine two claims. 10
- Classified as probably not a substantial claim. 6
May combine two claims.
PremisecitationThe APOE3Ch variant leads to less neurodegeneration and less cerebral amyloid angiopathy in the context of higher cortical amyloid burden than in PSEN1E280A carriers without APOE3Ch.
“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”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [7] Arboleda-Velasquez JF, Lopera F, O’Hare M, Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med 2019; 25: 1680– 3. 31686034 PMC6898984 sourceExperimental — accuracy not yet measured
- cites [8] Sepulveda-Falla D, Sanchez JS, Almeida MC, Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia. Acta Neuropathol 2022; 144: 589– 601. 35838824 PMC9381462 sourceExperimental — accuracy not yet measured
May combine two claims.
Premiseown dataThe original report of four APOE3Ch heterozygotes did not describe delayed cognitive impairment onset, leading the authors and others to first conclude that APOE3Ch heterozygosity was not protective.
“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.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [7] Arboleda-Velasquez JF, Lopera F, O’Hare M, Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med 2019; 25: 1680– 3. 31686034 PMC6898984 source
- cites [18] Cochran JN, Acosta-Uribe J, Esposito BT, Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred. Alzheimers Dement 2023; 19: 3835– 47. 36951251 PMC10514237 source
The Results at key APOE variants discuss a Christchurch case report and find a modest, nominally significant association with later age at onset. Our copy does not say that this paper initially concluded heterozygosity was not protective, or describe the original report’s four heterozygotes and their cognitive-impairment onset (searched: four heterozygotes, initial conclusion, protective effect). The paper’s current finding does not establish what its authors concluded initially. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim. May combine two claims.
PremisecitationCommon APOE variants affect Alzheimer's disease risk: APOE4 carries high risk, APOE3 is viewed as neutral, and APOE2 is relatively protective.
“Common variants of the apolipoprotein E gene (APOE) influence the risk of Alzheimer’s disease: APOE4 is linked to high risk, APOE3 is considered to confer a neutral risk, and APOE2 is associated with relative protection.2–5”
Quote in the paperSubstantial claim4 of 4 sources checked- cites [2] Strittmatter WJ, Saunders AM, Schmechel D, Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90: 1977– 81. 8446617 PMC46003 source
The allele-association passage reports that APOE-e4 was significantly more frequent in patients from families with Alzheimer’s disease than in controls, supporting its link to elevated risk in that setting. Table 1 also lists lower E2 frequency in patients than controls, but the paper does not establish that E2 is protective or characterize E3 as neutral. Its findings concern primarily late-onset familial Alzheimer’s disease, not Alzheimer’s disease generally. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [3] Corder EH, Saunders AM, Strittmatter WJ, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261: 921– 3. 8346443 source
Corder et al. (1993), “Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families,” is clearly relevant to the APOE4-risk portion of the claim. The paper-scoped search returned no snippets establishing that it also characterizes APOE3 as neutral and APOE2 as protective. Because the cited paper’s full text was unavailable and the sentence cites multiple sources (2–5), a match in another paper would not by itself establish misattribution. (LLM, conf=0.62)
Experimental — accuracy not yet measured - cites [4] Reiman EM, Arboleda-Velasquez JF, Quiroz YT, Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun 2020; 11: 667. 32015339 PMC6997393 sourceExperimental — accuracy not yet measured
- cites [5] Corder EH, Saunders AM, Risch NJ, Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet 1994; 7: 180– 4. 7920638 sourceExperimental — accuracy not yet measured
May combine two claims.
PremisecitationThe APOE3Ch variant is associated with less tau accumulation and less neuroinflammation in PSEN1E280A carriers.
“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”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [7] Arboleda-Velasquez JF, Lopera F, O’Hare M, Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med 2019; 25: 1680– 3. 31686034 PMC6898984 sourceExperimental — accuracy not yet measured
- cites [8] Sepulveda-Falla D, Sanchez JS, Almeida MC, Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia. Acta Neuropathol 2022; 144: 589– 601. 35838824 PMC9381462 sourceExperimental — accuracy not yet measured
May combine two claims.
Findingown dataAPOE3Ch heterozygotes had onset of mild cognitive impairment about 5 years later and onset of dementia about 4 years later than noncarriers.
“we found that they had an onset of mild cognitive impairment and dementia, analyzed retrospectively, that was approximately 5 years later for mild cognitive impairment and 4 years later for dementia”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTau pathology was within the expected range of variation and showed no visible association with age at dementia onset.
“Findings were within the expected range of tau deposition variation and without visible association between the extent of tau pathological findings and the age at onset of dementia (Table S4 and Fig. S6).”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe current analyses used a larger cohort and more thorough longitudinal clinical characterization than the original report.
“The analyses that we present here encompassed a larger cohort with APOE3Ch and PSEN1E280A variants, with more comprehensive longitudinal clinical characterization, and indicated that APOE3Ch heterozygosity is apparently linked to delay in the expected cognitive impairment.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataNeurologists and neuropsychologists who retrospectively classified participants did not know the participants' genetic variants.
“Using these data, neurologists and neuropsychologists, who were unaware of the genetic variants in the specific participants, retrospectively classified participants as having normal cognitive status, mild cognitive impairment, or dementia”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn this kindred, most PSEN1E280A carriers develop mild cognitive impairment around age 45 and dementia around age 50.
“Most of the carriers in this kindred have mild cognitive impairment in their mid-forties and dementia in their late forties.1”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol 2011; 10: 213– 20. 21296022 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenStaining for Alzheimer's disease pathological markers in cortical areas was done uniformly.
“Immunohistochemical staining was performed uniformly for pathological markers of Alzheimer’s disease in cortical areas, followed by quantitative morphologic evaluation of vascular pathologic features in all the participants.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataAPOE3Ch heterozygosity may protect against Alzheimer's disease and neurodegeneration in this population.
“The clinical, cognitive, neuroimaging, and neuropathological data that we present here provide evidence that APOE3Ch heterozygosity delayed the onset of cognitive impairment in a form of autosomal dominant Alzheimer’s disease and may have a protective effect against Alzheimer’s disease and neurodegeneration in this population.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataGroup balance before and after matching was checked with a standard mean or proportion difference.
“To examine the balance of the groups before and after matching, we used a standard mean (or proportion) difference (Fig. S3).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningThe protective effect of APOE3Ch observed in this Antioquia cohort may not extend to sporadic Alzheimer's disease or to other groups.
“Furthermore, the biologic insight that the APOE3Ch variant is protective in this group of persons from the Antioquia, Colombia, cohort may not translate to sporadic Alzheimer’s disease or to other groups.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataInvestigators did not know participants' genetic status while collecting data.
“During data collection, investigators were unaware of the genetic status of the participants.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The comparison between APOE3Ch carriers and noncarriers is not confounded by unmeasured factors.
“To control for potential confounding factors of sex, APOE genotype, and years of formal education, we established a matched sample between carriers and noncarriers of the APOE3Ch variant.”
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?
Heterozygous APOE3Ch carriers showed reduced cerebral amyloid angiopathy, attenuated parenchymal vascular abnormalities, and less microvessel fragmentation compared to typical PSEN1E280A cases.
“Post mortem studies revealed that the brain of a homozygous APOE3Ch carrier exhibited minimal astrocytic and microglial activation and clear vascular protection, while heterozygous carriers showed reduced cerebral amyloid angiopathy, attenuated parenchymal vascular abnormalities, and less microvessel fragmentation compared to typical PSEN1E280A cases. 3 , 11 , 12”
From Plasma extracellular vesicles from <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [3]
The Results section, “Pathological Findings in Persons with APOE3Ch” (page unavailable), reports less prominent cerebral amyloid angiopathy in the frontal cortex of carriers and vessel length, branching, and spacing more similar to controls than to PSEN1E280A noncarriers. These findings support reduced vascular pathology, but the passage does not specifically establish less microvessel fragmentation or characterize the abnormalities as parenchymal. (LLM, conf=0.82)
Experimental — accuracy not yet measuredNeuroimaging data revealed relatively preserved cortical structure with low tau accumulation in regions typically affected by early neurodegeneration in APOE3Ch carriers.
“Neuroimaging data further revealed relatively preserved cortical structure with low tau accumulation in regions typically affected by early neurodegeneration. 3”
From Plasma extracellular vesicles from <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [3]
The Results section (page not provided) reports a more limited tau burden in Alzheimer’s-related regions, including the entorhinal cortex, on PET imaging of one APOE3Ch heterozygote. It reports relatively preserved glucose metabolism in the imaged participants, not relatively preserved cortical structure. Structural MRI was performed, but the cited passages do not report a finding of preserved cortical structure. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPost mortem studies revealed that the brain of a homozygous APOE3Ch carrier exhibited minimal astrocytic and microglial activation and clear vascular protection.
“Post mortem studies revealed that the brain of a homozygous APOE3Ch carrier exhibited minimal astrocytic and microglial activation and clear vascular protection, while heterozygous carriers showed reduced cerebral amyloid angiopathy, attenuated parenchymal vascular abnormalities, and less microvessel fragmentation compared to typical PSEN1E280A cases. 3 , 11 , 12”
From Plasma extracellular vesicles from <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [3]
The Results section, “Pathological Findings in Persons with APOE3Ch” (page unavailable), reports less prominent cerebral amyloid angiopathy in carriers and vessel morphology more similar to controls than in PSEN1E280A carriers without APOE3Ch. It also reports less angiopathy in the previously studied homozygous carrier. It does not report minimal astrocytic or microglial activation, or explicitly characterize the vascular findings as reduced microvessel fragmentation. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe PSEN1E280A variant causes an aggressive form of ADAD, with carriers typically developing cognitive decline before age 47.
“Among these, the PSEN1E280A variant causes an aggressive form of ADAD, with carriers typically developing cognitive decline before age 47. 3”
From Plasma extracellular vesicles from <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [3]
The introductory passage following the Abstract says that autosomal dominant Alzheimer’s disease is nearly certain to develop in PSEN1E280A carriers and that most have mild cognitive impairment in their mid-forties. The Results report a median onset of approximately 47 years in matched carriers without APOE3 Christchurch, not an onset before 47; the claim’s precise age cutoff is therefore not established. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEvidence supports a protective role for APOE3Ch: homozygous carriers showed reversal of cerebral hypometabolism, and heterozygotes exhibited reduced angiogenesis and cerebral amyloid angiopathy.
“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 <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [3]
Citation 3 is attached to the claim about heterozygotes. The Results section, under “Pathological Findings in Persons with APOE3Ch” (page unavailable), reports less prominent cerebral amyloid angiopathy in APOE3Ch carriers than in noncarriers. It describes vessel shape and spacing but does not report reduced angiogenesis. (LLM, conf=0.88)
Experimental — accuracy not yet measured
A mildly protective effect of the heterozygous Christchurch mutation was found in the same kindred.
“A mildly protective effect of the heterozygous Christchurch mutation was also found in the same kindred25.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [25]
Similar to ApoE2, Christchurch (R136S) mutation is protective in autosomal dominant AD cases and AD mouse models.
“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 [25]
The rare ApoE R136S (Christchurch) variant is protective in the PSEN1 E280A kindred.
“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 [25]
A subsequent report suggested delayed onset even in heterozygotes in that kindred.
“and a subsequent report suggested delayed onset even in heterozygotes in that kindred 7 .”
From Association of Rare <i>APOE</i> Missense Variants R189C and W276C With Risk of Alzheimer Disease (2026) · cites this paper as [7]
Heterozygous APOE3Ch carriers exhibited a median 5-year delay in onset of MCI compared to non-carriers.
“Beyond this homozygous case, recent evidence indicates that heterozygous APOE3Ch carriers exhibited a median 5‐year delay in the onset of mild cognitive impairment (MCI) compared to non‐carriers.”
The PSEN1E280A mutation causes autosomal dominant Alzheimer's disease with predictable onset.
“The PSEN1E280A mutation causes autosomal dominant Alzheimer's disease (ADAD) with predictable onset, enabling presymptomatic studies.”
Multiple studies have demonstrated that APOECh mutation broadly suppresses gliosis, dampens inflammatory gene expression, and modulates DAM phenotypes in an amyloid and tau-context dependent manner.
“Multiple studies have demonstrated that APOECh mutation broadly suppresses gliosis, dampens inflammatory gene expression, and modulates disease-associated microglial (DAM) phenotypes in an amyloid and tau-context dependent manner [4, 5, 7, 42, 50].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [50]
The Results (Pathological Findings in Persons with APOE3Ch; page unavailable) describe greater amyloid burden and relatively limited tau burden in four heterozygous carriers, but do not report gliosis, inflammatory gene expression, or disease-associated microglial phenotypes. Searches for those terms and for amyloid- and tau-dependent microglial effects found no passage in the paper’s main text that addresses the attributed claim. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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Self-citationGenetic associations with age at dementia onset in the <i>PSEN1 E280A</i> Colombian kindred
Cochran, J. N., Acosta‐Uribe, J., Esposito, B. T., Madrigal, L., Aguillón, D., Giraldo, M. M., Taylor, J. W., Bradley, J., Fulton‐Howard, B., Andrews, S. J., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13021 · Cited by 21 · see citing works
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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 · see citing works
Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
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“Additional clinical studies from the Colombian cohort further revealed that individuals with one copy of the APOE ε3 Christ-church variant experienced a median delay of five years in disease onset compared to non-carriers [195].”
The impact of rare genetic variants on Alzheimer disease
Deyn, L. D., & Sleegers, K. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01062-1 · Cited by 43 · see citing works
“In the heterozygous state, this variant can also delay disease onset by several years 70 .”
Bashir, B., Gulati, M., Vishwas, S., Gupta, G., Dhanasekaran, M., Paudel, K. R., Chellappan, D. K., Anand, K., Negi, P., Singh, P. K., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102689 · Cited by 43 · see citing works
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“Whole-exome sequencing studies in these two cases suggest that a rare homozygous APOE variant ( APOE3 -Christchurch (p.Arg136Ser)) and a rare RELN variant (p.His3447Arg) conferred strong protection against the development of DIAD in these two PSEN1 p.Glu280Ala carriers 8,10,11 .”
Self-citationRecent advances in neuroimaging of Alzheimer's disease and related dementias
Ottoy, J., Owsicki, N., Bilgel, M., Binette, A. P., Salvadó, G., Kang, M. S., Cash, D. M., Ewers, M., Joie, R. L., Wisse, L. E. M., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70648 · Cited by 27 · see citing works
“167 The rare APOE ε 3 Christchurch ( APOE3 Ch ) variant (R136S) has been identified as protective in ADAD, 168,169 delaying neurodegeneration and tau PET uptake, even in the presence of A β PET positivity.”
Günaydin, C., Sondhi, D., Kaminsky, S. M., Lephart, H. C., Leopold, P. L., Hackett, N. R., Khanna, R., & Crystal, R. G. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.11.003 · Cited by 26 · see citing works
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“Examples of future tailored interventions include gene therapy for individuals with high genetic burdens (e.g., inspired by the Christchurch protective gene for the PSEN1 mutation) and multicomponent interventions (e.g., enhanced social interactions, physical activity, healthy diets, and medical monitoring) tailored f…”
A manifesto for Alzheimer’s disease drug discovery in the era of disease-modifying therapies
Hering, H., Bussière, T., Liu, C., Glajch, K. E., Weihofen, A., Grogan, J. L., & Walsh, D. M. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00872-7 · Cited by 26 · see citing works
“These and other human data [185], together with recent animal studies [175, 176], indicate that APOε3 - ch protects against the development of tau pathology.”
Protective genetic variants against Alzheimer's disease
Mariño, C., Malotaux, V., Giudicessi, A., Aguillon, D. F., Falla, D. S., Lopera, F. J., & Quiroz, Y. T. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00116-4 · Cited by 20 · see citing works
Self-citationNew insights into innate immunity in Alzheimer’s disease: From APOE protective variants to therapies
Chen, Y., & Holtzman, D. M. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.08.001 · Cited by 19 · see citing works
Age at onset of genetic disease and genetic dependent stage: evidence from cases with SCN1A variants
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Exosomal mRNA Signatures as Predictive Biomarkers for Risk and Age of Onset in Alzheimer’s Disease
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ApoE-calypse tau: ApoE–tau synergy in Alzheimer’s disease
Lennol, M. P., Bordier, C., Kamelher, L., Ulrich, J. D., Holtzman, D. M., & Gratuze, M. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20250965 · Cited by 14 · see citing works
Sex-related differences in genetically determined Alzheimer’s disease
Soriano, L. D. H., Wagemann, O., Bejanin, A., Levin, J., & Fortea, J. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1522434 · Cited by 13 · see citing works
Amyloid β, γ-secretase, and familial Alzheimer's disease
Potier, M., Steiner, H., & Chávez‐Gutiérrez, L. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00292-8 · Cited by 8 · see citing works
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A novel approach to resilience and its links with education and Alzheimer's disease genetics
Carrigan, M., Bocancea, D. I., Vogel, J. W., van Loenhoud, A. C., Tesi, N., Barkhof, F., Lucassen, P. J., van der Flier, W. M., Krugers, H. J., van der Lee, S. J., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70379 · Cited by 9 · see citing works
“8 For instance, a homozygous carrier of the APOE ε 3 Christchurch variant developed MCI nearlythree decadeslaterthanexpected, despiteAD-causative PSEN1 carriership and presence of amyloidosis.”
Gao, Y., Schedin‐Weiss, S., & Tjernberg, L. O. (2024) · Advanced technology in neuroscience . · doi:10.4103/atn.atn-d-24-00014 · Cited by 5 · see citing works
Eldik, L. J. V., Siemers, E., Collins, E. C., Gold, M., Henley, D. B., Johannsen, P., Möbius, H. J., Shulman, M. B., Zhou, J., Carrillo, M. C., et al. (2024) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70014 · Cited by 5 · see citing works
Pineda‐Lopez, L., Aguillon, D., Villar‐Vesga, J., Valderrama‐Carmona, P., Guerrero, A., Upreti, A., Arevalo‐Alquichire, S., Correa, L., Mendez‐Castellanos, K., Castaño, D., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71148 · Cited by 4 · see citing works
“3 Mechanistic studies demonstrate that the APOE3 Ch variant reduces binding to heparan sulfate proteoglycans (HSPGs), promoting cellular uptake and tau degradation and reducing tauopathy propagation.”
Self-citationThe Janus face of CaMKII: from memory consolidation to neurotoxic switch in Alzheimer’s disease
Tang, L., Liu, F., Sun, X., Yang, J., Liu, Y., Pan, X., Hao, L., Lou, F., & Su, J. (2025) · Archives of Toxicology · doi:10.1007/s00204-025-04160-7 · Cited by 5 · see citing works
Khani, M., Akçimen, F., Grant, S. M., Akerman, S. C., Lee, P. S., Faghri, F., Leonard, H. L., Kim, J. J., Makarious, M. B., Koretsky, M. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62108-y · Cited by 4 · see citing works
Recent Advances and Future Directions in Alzheimer’s Disease Genetic Research
Stancheva, M., Toncheva, D. I., & Karachanak-Yankova, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167819 · Cited by 4 · see citing works
“…populations, as recent genetic studies of Alzheimer’s disease in non-European populations have revealed both shared and population-specific risk factors [93], highlighting the importance of conducting further studies across diverse populations to identify ethnic-specific polymorphisms [86].”
Quiroz, Y. T., Aguillon, D. F., Arboleda‐Velásquez, J. F., Bocanegra, Y., Cardona‐Gómez, G. P., Corrada, M. M., Diez, I. P., Garcia-Cifuentes, E. R., Kosik, K. S., Martinez, L., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70037 · Cited by 2 · see citing works
“16,17 These results underscore the significance of Notch3 signaling in maintaining gliovascular coupling, which supports vascular protection andhomeostasis.”
Self-citation<i>APOE3</i> Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease
(2024) · New England Journal of Medicine · doi:10.1056/nejmc2409320 · Cited by 3 · see citing works
Kryukova, O. V., Islanov, I. O., Zaklyazminskaya, E. V., Korostin, D. O., Belova, V., Cheranev, V. V., Repinskaia, Z. A., Tonevitskaya, S. A., Petukhov, P. A., Dudek, S. M., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12102410 · Cited by 3 · see citing works
“Analogous protecting mutations ( RELN (H3447R) and APOECh (R136S)) were recently reported in carriers of PSEN-1 E280A mutations, which delayed the development of mild cognitive impairment and dementia in carriers of this PSEN1 mutation for about 20 years [45,46].”
BackgroundCarter, R. C., Yang, Z., Akkaya-Hocagil, T., Jacobson, S. W., Jacobson, J. L., Dodge, N. C., Hoyme, H. E., Zeisel, S. H., Meintjes, E. M., Kızıl, Ç., et al. (2024) · Gene · doi:10.1016/j.gene.2024.148854 · Cited by 3 · see citing works
Protection against Alzheimer’s Disease with APOE Christchurch Variant — How?
Hardy, J. (2024) · New England Journal of Medicine · doi:10.1056/nejme2403712 · Cited by 5 · see citing works
Georgiadou, D., & Chroni, A. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149644 · Cited by 2 · see citing works
Khani, M., Akçimen, F., Grant, S. M., Åkerman, S., Lee, P. S., Faghri, F., Leonard, H. L., Kim, J. J., Makarious, M. B., Koretsky, M. J., et al. (2024) · medRxiv · doi:10.1101/2024.11.03.24313587 · Cited by 2 · see citing works
Patel, M., Feng, W., McKay, N. S., Millar, P. R., Liu, M., Yang, C., Cetin, A., Johnson, M., Budde, J., Western, D., et al. (2026) · The Lancet Neurology · doi:10.1016/s1474-4422(26)00123-7 · Cited by 1 · see citing works
“6,7 Whereas the APOE Christchurch and RELN variants were protective, individuals carrying an ADAD mutation and one of these newly identified common risk alleles face an even higher risk of developing Alzheimer’s disease compared with non-risk allele carriers.”
Protective mutations associated with APOE in Alzheimer’s disease
Ma, Y., Li, Y., Wu, G., Liu, L., Tian, M., Han, X., Chen, X., Xuan, X., Zheng, T., Gao, X., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03496-5 · Cited by 1 · see citing works
“A recent human case report described that individuals with both the PSEN1 - E280A and APOE3ch mutations experience cognitive decline approximately 5 years later than those with only the PSEN1 - E280A mutation [42].”
APOE, Inflammation, and T Cells in Translational Disease Models and Clinical Medicine
Adlimoghaddam, A., Cervantes, D., & Wheeler, C. J. (2026) · Springer eBooks · doi:10.1007/978-3-031-96089-5_35 · Cited by 1 · see citing works
de Magalhães, C. G., Moldakozhayev, A., Lopez, M. V., Bowman, G. L., Chhatwal, J. P., Kellis, M., Mohs, R. C., Nisenbaum, L., Quiroz, Y. T., Raju, R. M., et al. (2025) · Aging Cell · doi:10.1111/acel.70351 · Cited by 2 · see citing works
“Her team emphasized the importance of establishing baseline levels of pTau217 and other biomarkers decades before symptom onset, while also uncovering resilience variants such as APOE3 Christchurch , which can delay cognitive decline despite amyloid accumulation (Quiroz et al. 2024).”
Self-citationZuo, Y., Ding, X., Sun, Y., Wang, L., Song, Y., Zhao, Z., & Liu, C. (2025) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2025.123734 · Cited by 1 · see citing works
Clonal hematopoiesis as the intersection between genetics and resilience in Alzheimer’s disease
López-de-Mesa-Aragón, J., Silva‐Buriticá, C., & Salazar‐Londoño, S. (2025) · npj Dementia · doi:10.1038/s44400-025-00014-2 · Cited by 1 · see citing works
Mahley, R. W. (2025) · Springer eBooks · doi:10.1007/978-3-031-52641-1_2-1 · Cited by 1 · see citing works
Astrocytic synapse engulfment is differentially controlled by APOE genotype
Sekizar, S., Holt, K., Meyers, S., Tzioras, M., King, D., Tulloch, J., Jackson, R. J., & Spires‐Jones, T. L. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.09.026
Plasma Biomarker Profiles in a Colombian Cohort of Heterozygous APOE3-Christchurch CarriersPreprint
Malotaux, V., Tristão‐Pereira, C., Zuluaga, Y., Muñoz, C., Guerrero, A., Bocanegra, Y., Alzate, D., Serna, L., Guzmán, C., Ospina, C., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10705602/v1
Self-citationToward personalized medicine in AD/ADRD through genetic-exposome dementia risk assessments
Tolosa‐Tort, P., Okorie, M., Chatterjee, A., Boeriu, A. I., Sharma, R. U., & Andrews, S. J. (2026) · npj Dementia · doi:10.1038/s44400-026-00087-7
“A similar, though less pronounced delay has been observed in heterozygous APOE * ε 3 Christchurch carriers, although this observation remains under active investigation 38,39 .”
Rebeck, G., Shautidze, G., Sepulveda, J., Healey, G., & Narayan, P. S. (2026) · Glia · doi:10.1002/glia.70193
Genetic modifiers in autosomal dominant Alzheimer's disease
Kosik, K. S. (2026) · The Lancet Neurology · doi:10.1016/s1474-4422(26)00168-7
Self-citationAssociation of Rare <i>APOE</i> Missense Variants R189C and W276C With Risk of Alzheimer Disease
Le Guen, Y., Reil, D., Jackson, R. J., Peña-Tauber, A., Khosla, C., & Greicius, M. D. (2026) · doi:10.64898/2026.05.08.26352778
Revisiting Founder Populations in an Age of Global Biobanks
Caggiano, C., Shemirani, R., & Kenny, E. E. (2026) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-020525-034901
Tang, J.-Y., Tan, Q., Yu, Z.-Y., Yuan, Z.-Y., Zeng, R., Liu, X.-Y., Zhu, X.-Y., Zhao, Y., Li, J.-H., Bai, Y.-D., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.04.027
Alzheimer disease protection from the periphery
Wang, K., & Bu, G. (2026) · Nature Reviews Neurology · doi:10.1038/s41582-026-01211-0
Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice
Raulin, A.-C., Alnobani, A., Rodriguez-Martinez, P., Lee, E., Linares, C., Yslas, A. R., Li, M., Ren, Y., Doss, S. V., Roy, B., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04002-9
“All other data are available from the corresponding author upon reasonable request.”
Li, H., Liu, S., Miao, D., Chen, L., Sun, Y., Wang, G., Zhu, Z., Li, X., & Lu, Q. (2026) · iScience · doi:10.1016/j.isci.2026.115456
A critical appraisal of the link between apolipoprotein E and Tau
Das, S., Hyman, B. T., & Serrano‐Pozo, A. (2026) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001459
APOE, Inflammation, and T Cells in Translational Disease Models and Clinical Medicine
Adlimoghaddam, A., Cervantes, D., & Wheeler, C. J. (2026) · Springer eBooks · doi:10.1007/978-3-031-52641-1_35-1
Mahley, R. W. (2026) · Springer eBooks · doi:10.1007/978-3-031-96089-5_2
Alzheimer’s Disease: Progress in Biomarkers, Diagnostics and Therapies
Wilson, E. N., Sommer, B., Scheltens, P., & Nikolich, K. (2026) · Springer eBooks · doi:10.1007/978-3-032-31497-0_8
Fang, H., Tang, A., Tang, C., et al. (2025) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000006238
APOE2 reduces risk of Alzheimer's disease by protection of lysosomes from lipid overloading
Feng, J., Ma, X., & Ye, J. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.03.001
Blasi, M. T., Borioni, M. S., Nuti, F., Belvisi, D., Canevelli, M., Fabbrini, G., & Bruno, G. (2025) · Case Reports in Neurological Medicine · doi:10.1155/crnm/8251065
“Furthermore, APOE genotyping has been shown to infuence the clinical expression and, potentially, the radiological phenotype of PSEN-1-related Alzheimer’s disease [9].”
Vastrad, B. M., & Vastrad, C. M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.03.626535 · Cited by 1 · see citing works
In memoriam: Francisco Javier Lopera Restrepo (10 de junio de 1951 – 10 de septiembre de 2024)
Pineda, D. A. (2024) · Acta neurológica colombiana · doi:10.22379/anc.v40i4.1261
Ibáñez, A. M., Bateman, R. J., & Santamaría‐García, H. A. (2024) · Nature Aging · doi:10.1038/s43587-024-00735-8
Single Copy of APOE3 Christchurch Variant Slows Cognitive Impairment by 5 Years
Hurley, D. (2024) · Neurology Today · doi:10.1097/01.nt.0001027356.90203.9c
- Authors
- 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., Posada-Duque, R., Littau, J. L., Villalba-Moreno, N. D., Vila-Castelar, C., Ramirez Gomez, L., Garcia, G., Kaplan, E., Rassi Vargas, S., Ossa, J. A., Valderrama-Carmona, P., Perez-Corredor, P., Krasemann, S., Glatzel, M., Kosik, K. S., Johnson, K., Sperling, R. A., Reiman, E. M., Sepulveda-Falla, D., Lopera, F., & Arboleda-Velasquez, J. F.
- Affiliations
- Brigham and Women's Hospital (US)
- From Massachusetts General Hospital (Y.T.Q., J.S.S., S.L., C.V.-C., L.R.G., E.K., K.J., R.A.S.), the Departments of Neurology (Y.T.Q., J.S.S., L.R.G., K.J., R.A.S.), Psychiatry (Y.T.Q., S.L., C.V.-C., E.K.), and Ophthalmology (P.P.-C., J.F.A.-V.), Harvard Medical School, Brigham and Women’s Hospital (K.J., R.A.S.), and Schepens Eye Research Institute, Mass Eye and Ear (P.P.-C., J.F.A.-V.) — all in Boston; Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia (Y.T.Q., D.A., D.C.A-A., D.V., Y.Z., A.Y.B., L.M., L.H., R.P.-D., G.G., S.R.V., J.A.O., P.V.-C., F.L.); the Institute of Neuropathology, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.L.L., N.D.V.-M., S.K., M.G., D.S-F.); the Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, Santa Barbara (K.S.K.); and the Banner Alzheimer’s Institute, Phoenix, the University of Arizona, Tucson, and Arizona State University...
- ORCID
- Quiroz, Yakeel T.
- Aguillon, David
- Vasquez, Daniel
- Zuluaga, Yesica
- Baena, Ana Y.
- Hincapié, Liliana
- Sanchez, Justin S.
- Langella, Stephanie
- Littau, Jessica L.
- Perez-Corredor, Paula
- Krasemann, Susanne
- Glatzel, Markus
- Kosik, Kenneth S.
- Johnson, Keith
- Sperling, Reisa A.
- Reiman, Eric M.
- Sepulveda-Falla, Diego
- Lopera, Francisco
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2024-06-20
- Volume
- 390
- Issue
- 23
- Pages
- 2156-2164
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC12640232
- OpenAlex
- W4399797682
- Cited by
- 63
- References
- 18
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 16
- FWCI
- 17.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- autosomal dominant Alzheimer's disease, dementia onset, tau imaging, FDG-PET, vascular amyloid, familial kindred, Antioquia, apolipoprotein E
- MeSH terms
- Adult, Aged, Alzheimer Disease, Brain, Colombia, Family, Female, Genes, Dominant, Heterozygote, Humans, Male, Middle Aged, Retrospective Studies, Age of Onset, Positron-Emission Tomography, Apolipoprotein E3, Presenilin-1
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