The DOI matches its Crossref record; 25 of the 26 references it cites were found in a registry or an index; none of the 23 sources its claims cite is checked for support yet.
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Open accessAbstract
Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.
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18 Not checked yet · 15 Own result · 10 Own interpretation · 1 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The alele frequency of the APOE-e4 in 30 random affected patients, each from a different Azheimer disease family, was 0.50 t 0.06;”
- Also stated in: § MATERIALS AND METHODS · plain
“the frequency of the APOE-e4 allele in the 30 patients (0.50 ± 0.06)”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
plainn = 30 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“The allele frequency of APOE-E4 found in our control population was similar to that found in a larger population study (20).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [20] 20. Menzel, J., Kladetzky, K. G. & Assmann, G. (1983) Arterio- sclerosis 4, 310-315.
plainn = 91- Asserted: passes — The authors put it forward as true.
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In the paper
“the aUlele frequency of APOE-e4 in 91 age-matched unrelated controls was 0.16 ± 0.03 (Z = 2.44, P = 0.014).”
- Also stated in: § MATERIALS AND METHODS · plain
“differed significantly from the frequency found in the 91 controls (0.16 ± 0.03; Z = 2.44, P = 0.014).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
plaincorrelationaln = 30 ·- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The 91 unrelated CEPH grandparents used as controls are genetically comparable to the familial Alzheimer disease cases, so the allele frequency difference is not due to population stratification.
- Rests on an assumption: The two early-onset families in the sample do not materially affect the association between APOE-e4 and late-onset familial Alzheimer disease.
- Also stated in: § MATERIALS AND METHODS · plain
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In the paper
“the aUlele frequency of APOE-e4 in 91 age-matched unrelated controls was 0.16 ± 0.03 (Z = 2.44, P = 0.014).”
- Also stated in: § MATERIALS AND METHODS · plain
“the frequency found in the 91 controls (0.16 ± 0.03; Z = 2.44, P = 0.014).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
plainn = 91 ·- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The 91 unrelated CEPH grandparents used as controls are genetically comparable to the familial Alzheimer disease cases, so the allele frequency difference is not due to population stratification.
- Also stated in: § MATERIALS AND METHODS · 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
“ApoE in CSF remained bound to immobilized (A4-(1-40), fA4-(1-28), andj'A4-(12-28) after incubation and washing with phosphate-buffer saline plus 5% SDS.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
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In the paper
“This contaminant protein was identified by protein microsequenc- ing to be ApoE.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
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“ApoE immunoreactivity (Fig. 4B) closely imitated the distribution of 3A4 amyloid (Fig. 4C), even being observed near glial processes (Fig. 4 B and C, arrowheads).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
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In the paper
“This peptide also bound ApoE after washing with phosphate- buffered saline plus 5% SDS (Fig. 2).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“ApoE did not bind to this immobilized peptide (Fig. 2 Lower).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic 13A4 peptide (the primary constituent of the senile plaque) with high avidity.”
- Also stated in: § MATERIALS AND METHODS · boosted
“Using this technique, we have demonstrated high-avidity binding of ApoE in CSF to ,BA4 peptide.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 12
- Probably not a substantial claim. 19
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
“Apolipoprotein E is immunochemically local- ized to the senile plaques, vascular amyloid, and neuroflbrillary tangles of Alzheimer diwase.”
- Also stated in: § MATERIALS AND METHODS · plain
“Antiserum to ApoE stained amyloid plaques in tissues from Alzheimer disease patients and an aged lemur (Fig. 4 B and E).”
- Also stated in: § MATERIALS AND METHODS · plain
“ApoE is found in senile plaques, in neurofibrillary tangles, and-at the sites of congophilic angiopathy of Alzhei- mer disease”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § MATERIALS AND METHODS · 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
“Antiserum to ApoE stained amyloid plaques in tissues from Alzheimer disease patients and an aged lemur (Fig. 4 B and E).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Using the in vitro assay described here, we found that antithrombin, a related protein, did not bind the fA4 peptide but a contaminant protein did.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Guanidine hydrochloride did not elute ApoE from the 3A4-(12-28) peptide but did elute virtually all the ApoE bound to the even-hydropathy control peptide (Fig. 1 Lower, lanes 4).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There are three major isoforms of ApoE identified by amino acid sequencing, designated ApoE-E3, ApoE-E4, and ApoE-E2.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [1] 1. Mahley, R. W. (1988) Science 240, 622-628.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“APOE mRNA is increased severalfold in the brain of patients with Alzheimer disease and in the brain of animals with scrapie (10), a transmissible disease in animals that is similar to Creutzfeld-Jakob disease in humans and also exhibits prion protein plaques (9).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [10] 10. Diedrich, J. F., Minnigan, H., Carp, R. I., Whitaker, J. N., Race, R., Frey, W., II, & Haase, A. T. (1991) J. Virol. 65, 4759-4768.
- Not checked yetcites [9] 9. Prusiner, S. B., Hsiao, K. K., Bredesen, D. E. & DeArmond, S. J. (1989) in Handbook of Clinical Neurology, ed.
plaindirect- 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.
In the paper
“ApoE is also bound in the amyloid plaques of another dementing degenerative disease, Creutzfeld-Jakob disease (8).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [8] 8. Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E. & Ikeda, K. (1991) Brain Res. 541, 163-166.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“With the recent appreciation that 3A4 amyloid is a normal extracellular product in many cell types (26), the discovery of specific interactions between ApoE and ,SA4 could define additional mechanisms of Alz- heimer disease pathogenesis.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [26] 26. Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B. & Selkoe, D. J. (1992) Science 359, 322-325.
hedgedconditional- 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.
- Rests on an assumption: In vitro binding of ApoE to synthetic beta-A4 peptides reflects a biologically relevant interaction that occurs in vivo.
In the paper
“ApoE-E4 contains an arginine at residue 112, whereas E3 has a cysteine.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [1] 1. Mahley, R. W. (1988) Science 240, 622-628.
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. It may state two separate claims as one.
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In the paper
“APOE-e4 frequency was similar for all 83 tested Alzheimer disease patients in the 30 families, indicating that the random sample used in the association analysis accurately represented the e4 allele frequency in the families (Table 1).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
hedgedn = 83- 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
“Second, there could also be another intragenic polymorphism on an APOE-e4 background that confers susceptibility to Alzheimer disease.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
hedgedconditional- 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 may give no reason why it holds.
In the paper
“The gene for apolipo- protein E is located on chromosome 19q13.2,within the region previously associated with linkage of late-onset familial Alz- heimer diseas.”
- Also stated in: § MATERIALS AND METHODS · plain
“APOE is on the proximal long arm of chromosome 19, at 19q13.2 (1).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [1] 1. Mahley, R. W. (1988) Science 240, 622-628.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Also stated in: § MATERIALS AND METHODS · plain
In the paper
“The amyloid deposits in Creutzfeld-Jakob disease contain the prion protein, not the 3A4 peptide in Alzheimer disease (9).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [9] 9. Prusiner, S. B., Hsiao, K. K., Bredesen, D. E. & DeArmond, S. J. (1989) in Handbook of Clinical Neurology, ed.
plain- 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
“A function involving the binding, transport, and targeting of 83A4 (or other peptides) may link the diagnostic lesions and genetic susceptibility, suggesting a functional role for ApoE isoforms in the mechanism of Alzheimer disease pathogenesis.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: In vitro binding of ApoE to synthetic beta-A4 peptides reflects a biologically relevant interaction that occurs in vivo.
In the paper
“In addition, intraneuronal staining was observed, which may represent staining of neurofibrillary tangles (8) or early degeneration of neurons (Fig. 4 D-F).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [8] 8. Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E. & Ikeda, K. (1991) Brain Res. 541, 163-166.
hedgedconditional- 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.
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In the paper
“PCR-based restriction isotyping ofAPOE alleles has been developed for use in population'studies (13, 14).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [13] 13. Wenham, P. R., Price, W. H. & Blundell, G. (1991) Lancet 337, 1158-1159.
- Not checked yetcites [14] 14. Hixson, J. E. & Vernier, D. T. (1990)J. LipidRes. 31, 545-548.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Brain contains large quantities ofAPOE mRNA, second only to the liver (5).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [5] 5. Elshourbagy, N. A., Liao, W. S., Mahley, R. W. & Taylor, J. M. (1985) Proc. Natl. Acad. Sci. USA 82, 203-207.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Several additional proteins are asso- ciated with 13A4, including ApoE, APP, a1-antichymotrypsin, complement factors, and immunoglobulins (12).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [12] 12. Beyreuther, K. & Masters, C. L. (1991) Brain Pathol. 1, 241-251.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“ApoE-E2 contains a cysteine at residue 158, whereas E3 has an arginine.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
What the sources say
- Not checked yetcites [1] 1. Mahley, R. W. (1988) Science 240, 622-628.
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. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The association of the APOE-e4 allele with familial Alzheimer disease was significantly increased compared to the population controls and is consistent with prior analyses.”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > MATERIALS AND METHODS
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“After crush injury to the central nervous system optic nerve, ApoE is bound to the degenerating optic tracts and to the retino-recipient layers of the lateral geniculate nucleus and the superior colliculus (7).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [7] 7. Snipes, G. J., McGuire, C. B., Norden, J. J. & Freeman, J. A. (1986) Proc. Nat!. Acad. Sci. USA 83, 1130-1134.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“ApoE is pro- duced and secreted in the central nervous systram by astro- cytes (2-4).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [2] 2. Ignatius, M. J., Gebicke-Harter, P. J., Skene, J. H. P., Schill- ing, J. W., Weisgraber, K. H., Mahley, R. W. & Shooter, E. M. (1986) Proc. Natl. Acad. Sci. USA 83, 1125-1129.
- Not checked yetcites [3] 3. Boyles, J., Pitas, R. E., Wilson, E., Mahley, R. W. & Taylor, J. M. (1985) J. Clin. Invest. 76, 1501-1513.
- Not checked yetcites [4] 4. Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D. & Mahley, R. W. (1987) Biochim. Biophys. Acta 917, 148-161.
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.
None of the sources cited for this claim have been checked yet.
In the paper
“In the peripheral nervous system, the synthesis of ApoE increases 250-to 350-fold within 3 weeks of sciatic nerve crush, and ApoE constitutes 5% of the total soluble extracellular protein (2, 6).”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [2] 2. Ignatius, M. J., Gebicke-Harter, P. J., Skene, J. H. P., Schill- ing, J. W., Weisgraber, K. H., Mahley, R. W. & Shooter, E. M. (1986) Proc. Natl. Acad. Sci. USA 83, 1125-1129.
- Not checked yetcites [6] 6. Boyles, J. K., Zoellner, C. D., Anderson, L. J., Kosik, L. M., Pitas, R. E., Weisgraber, K. H., Hui, D. Y., Mahley, R. W., Gebicke-Haerter, P. J., Ignatius, M. J. & Shooter, E. M. (1989) J. Clin. Invest. 83, 1015-1031.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“These pro- teins, as well as the ,BA4 amyloid peptide, are also found surrounding cerebral vessels in Alzheimer disease, producing the”
§ Apolipoprotein E: High-avidity binding to ,B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease > Abstract
What the sources say
- Not checked yetcites [12] 12. Beyreuther, K. & Masters, C. L. (1991) Brain Pathol. 1, 241-251.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
In vitro binding of ApoE to synthetic beta-A4 peptides reflects a biologically relevant interaction that occurs in vivo.
“Using this technique, we have demonstrated high-avidity binding of ApoE in CSF to ,BA4 peptide.”
The paper relies on this without support.
The 91 unrelated CEPH grandparents used as controls are genetically comparable to the familial Alzheimer disease cases, so the allele frequency difference is not due to population stratification.
“Controls used in the study were 91 unrelated grandparents from the Centre d'Etude du Polymorphisme Humain (16).”
The paper relies on this without support.
The two early-onset families in the sample do not materially affect the association between APOE-e4 and late-onset familial Alzheimer disease.
“In 28 of the families the disease was of the late-onset type (mean age of onset >60 years of age), and in 2 of the families, early onset (mean age of onset < 60 years of age).”
The paper relies on this without support.
Localization of ApoE to Alzheimer disease lesions indicates a functional pathogenetic role rather than a secondary or incidental association.
“The ldcalization of ApoE to the defining pathological lesions of Alzheimer disease suggests a functional pathogenetic role for ApoE.”
The paper relies on this without support.
The synthetic beta-A4 peptide fragments used in the binding assay reproduce the relevant structural features of native beta-A4 in senile plaques.
“Preparation of Immobilized Peptides.fA4 peptides (Bachem) and other peptides were covalently immobilized on Immobilon AV affmity membrane (Millipore).”
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
“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”
From APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease (2024) · 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
“APOE4 is the strongest genetic risk factor for Alzheimer’s disease (AD)1–3.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · 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
“Apolipoprotein E ε4 (APOE ε4) is the strongest genetic risk factor for Alzheimer’s disease (AD).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Strittmatter et al., 1993
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 APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD).”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [8]
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 APOE4 allele is a major genetic risk factor for late-onset AD and was previously shown to accelerate AD progression in humans and in mouse models 6-11 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [8]
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
“Importantly, the APOE4 variant is the largest monogenetic risk factor for Alzheimer’s disease, while APOE2 is protective1,2.”
From Common germline variants of the human APOE gene modulate melanoma progression and survival (2020) · 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
“Among these genes, apolipoprotein E ( APOE ; especially the APOE ε 4 allele) is the highest genetic risk factor for LOAD [23,24].”
From Is there a role for B cells in Alzheimer's disease? (2026) · 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
“It exacerbates AD-related pathologies, including amyloid-beta (Aβ) plaques, Tau tangles, neurodegeneration and neuroinflammation4–16.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [12]
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 ɛ2 and ɛ3 bind to Aβ; however, this is lost in the apoE ɛ4 variant [11, 12].”
From Discovery of a Missense Mutation (Q222K) of the APOE Gene from the Australian Imaging, Biomarker and Lifestyle Study (2023) · cites this paper as [12]
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 APOE4 variant of apolipoprotein E was identified 30 years ago as the major genetic risk factor for Alzheimer’s Disease (AD) at the population level (Bennett et al, 2009; Corder et al, 1993; Strittmatter et al, 1993)”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Strittmatter et al, 1993
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 ε-4 isoform of apoE is the strongest molecular risk factor for the development of AD. About 60–80% of AD patients have at least one copy of apoE4 [2], [4], [5] and the risk for AD is increased in an ε-4 allele dose-dependent manner [6].”
From LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease (2010) · 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
“The apolipoprotein E gene (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) with the ε4 allele increasing and the ε2 allele decreasing AD risk relative to the ε3 allele (Holtzman et al., 2012; Strittmatter et al., 1993).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Strittmatter et al., 1993
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 is the most important genetic risk factor for sporadic AD (Corder et al., 1993; Strittmatter et al., 1993).”
From The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-β Peptide in the Brain (2013) · cites this paper as Strittmatter et al., 1993
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, apoE and apoJ form stable complexes with A (11, 16 -20), alter the aggregation of various A peptides (21)(22)(23), and affect A neurotoxicity (24 -27).”
From Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures (2000) · cites this paper as [11]
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
“with one copy of the APOE4 allele increasing disease risk by about 4-fold and two copies increasing disease risk by about 12-fold relative to the most prevalent APOE3 allele (7, 8).”
From Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform (2026) · cites this paper as [7]
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 is the most important genetic risk factor for late-onset Alzheimer’s disease (AD)”
From Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform (2026) · cites this paper as [7]
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
“with one copy of the APOE4 allele increasing disease risk by about 4-fold and two copies increasing disease risk by about 12-fold relative to the most prevalent APOE3 allele (7, 8).”
From Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform (2026) · cites this paper as [7]
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, apoE, specifically the e4 subtype (apoE4), is the strongest genetic risk factor associated with sporadic AD (28, 29).”
From Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol (2021) · cites this paper as [28]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Consistent with APOE’s biological function2–6, APOE4 significantly altered signaling pathways associated with cholesterol homeostasis and transport.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“APOE exists as three polymorphic alleles (APOE2, APOE3, APOE4) which encode three protein isoforms (apoE2, apoE3, and apoE4) distinguished by single amino acid substitutions at positions 112 and 158”
From Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement (2027) · cites this paper as Strittmatter et al., 1993
In the citing paper
“APOE is the strongest genetic risk factor for LOAD”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Strittmatter et al., 1993
In the citing paper
“Variants of the apolipoprotein E allele appear to account for most cases of late-onset Alzheimer's disease”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [1]
In the citing paper
“the e4 allele has been associated with an increased risk of Alzheimer's disease, 1-7”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [1]
In the citing paper
“Inheritance of the e4 allele of APOE is the only well-established genetic risk factor for sporadic AD (147).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [147]
In the citing paper
“expression of the ApoE4 allele, a major risk factor for sporadic AD (Corder et al., 1993; Schmechel et al., 1993; Strittmatter et al., 1993), may be involved.”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Strittmatter et al., 1993
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Consistentz = 2.44reported p = .014 · recomputed p = .015
“(Z = 2.44, p = .014”
- Consistentz = 2.44reported p = .014 · recomputed p = .015
“Z = 2.44, p = .014”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
Citations
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“The earliest identified and most significantly associated genetic risk factor for sAD is the E4 allele of the APOE which markedly increases AD risk relative to the APOE3 allele, while the APOE2 allele is considered protective (Corder et al., 1993; Lambert et al., 2013; Strittmatter et al., 1993).”
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“This risk allele, which was discovered in 1993 by Strittmatter, Roses and colleague”
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“The APOE 4 allele is associated with increased cerebral and vascular A deposition in AD (25), and the ApoE E4 isoform is associated with increased A binding, fibrillization, and cerebral and vascular A deposition (13, 26), as well as with decreased ApoE-mediated A clearance and degradation (27–29).”
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Metadata
- Authors
- Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D.
- Affiliations
- Duke University (US)
- Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-03
- Volume
- 90
- Issue
- 5
- Pages
- 1977-1981
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC46003
- OpenAlex
- W2021181758
- Cited by
- 4,268
- References
- 26
- Citations by year
- 2026: 67 · 2025: 107 · 2024: 97 · 2023: 108 · 2022: 99 · 2021: 106 · 2020: 116 · 2019: 111 · 2018: 117 · 2017: 104 · 2016: 121 · 2015: 140 · 2014: 123 · 2013: 112 · 2012: 134
- FWCI
- 125.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r35ag007922-07)
- National Institute on Aging (5P50 AG-O5128, P50AG005128, 5R35 AG-O7922)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE ε4, amyloid-beta, amyloid plaques, amyloid binding, allele frequency, genetic association, Alzheimer disease pathogenesis
- MeSH terms
- Alleles, Alzheimer Disease, Amino Acid Sequence, Animals, Apolipoproteins E, Brain, Gene Frequency, Humans, Lemur, Molecular Sequence Data, Peptides, Protein Binding, Solubility, Amyloid beta-Peptides
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