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Cited by 84Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchLipoproteins and Cardiovascular Health

Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1polymorphisms

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Wahrle, Suzanne E, Shah, Aarti R, Fagan, Anne M, Smemo, Scott, Kauwe, John SK, Grupe, Andrew, Hinrichs, Anthony, Mayo, Kevin +4 more·2007·Molecular Neurodegeneration
DOI 10.1186/1750-1326-2-7PMC PMC1857699
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Abstract

Background: Animal studies suggest that brain apolipoprotein E (apoE) levels influence amyloid-β (Aβ) deposition and thus risk for Alzheimer's disease (AD). We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1) in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF) apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs). Results: In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r 2 = 0.93, p < 0.01). In contrast, CSF apoE levels in different individuals varied widely (coefficient of variation = 46%). CSF apoE levels did not vary according to AD status, APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r 2 = 0.05, p = 0.003). We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported. Conclusion: We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set.

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  • Human CSF ApoE concentrations are ~7-9 μg/ml (~206-265 nM).

    “Human CSF ApoE concentrations were reported to be ~7–9 μg/ml (~206–265 nM)”

    From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [47]

    The Results section (“ApoE levels and stability in human CSF”; page unavailable) reports a mean of 9.09 μg/ml in 168 subjects, supporting the approximate 9 μg/ml figure. It does not report 7–9 μg/ml as a range or give concentrations in nM; the Discussion instead reports an observed range of 2–16 μg/ml. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The concentrations of ApoE found in the brain are similar to the concentrations we found to be effective in cell culture.

    “The concentrations of ApoE found in the brain are similar to the concentrations we found to be effective in cell culture.16”

    From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [16]

    The Results and Discussion report human cerebrospinal-fluid ApoE concentrations averaging 9.09 μg/ml and ranging from 2 to 16 μg/ml. The paper does not report concentrations measured in brain tissue; the comparison with effective cell-culture concentrations is the citing authors’ own finding, not one this source can establish. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • More recent studies also report that CSF apoE concentrations, measured by apoE ELISA and nephelometry, do not significantly differ among subjects with different apoE isoforms.

    “More recent studies also report that CSF apoE concentrations, measured by apoE ELISA and nephelometry, do not significantly differ among subjects with different apoE isoforms (Bekris et al., 2008; Wahrle et al., 2007).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Wahrle et al., 2007

    The Results section reports no significant difference in CSF apoE levels among subjects with different APOE genotypes, and the Methods section describes measuring CSF apoE by ELISA. The cited paper does not report using nephelometry, so it supports the finding and one of the two stated measurement methods, but not the full sentence as attributed to it. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • LNP uptake reached saturation at ~5 μg ApoE/ml.

    “We found that LNP uptake reached saturation at ˜5 µg ApoE/ml (Figure 3c), in line with measurements from human cerebrospinal fluid (CSF) in vivo of 9.09 µg/ml.16”

    From Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain (2013) · cites this paper as [16]

  • The levels of CSF apoE were not significantly different between cognitively normal subjects (CDR 0) and those who had very mild (CDR 0.5) or mild-moderate dementia (CDR 1-2).

    “The levels of CSF apoE were not significantly different between cognitively normal subjects (CDR 0) and those who had very mild (CDR 0.5) or mild-moderate dementia (CDR 1–2).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Wahrle et al., 2007

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Research works printed but not linked: 54

  1. Raber J Huang Y Ashford JW ApoE genotype accounts for the vast majority of AD risk and AD pathology Neurobiol Aging 2004 25 641 650 15172743 10.1016/j.neurobiolaging.2003.12.023 · DOI · Paper page
  2. Strittmatter WJ Saunders AM Schmechel D Pericak-Vance M Enghild J Salvesen GS Roses AD 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 1981 8446617 10.1073/pnas.90.5.1977 PMC46003 · DOI · Paper page
  3. Corder EH Saunders AM Strittmatter WJ Schmechel DE Gaskell PC Small GW Roses AD Haines JL Pericak-Vance MA Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families Science 1993 261 921 923 8346443 10.1126/science.8346443 · DOI · Paper page
  4. Mayeux R Stern Y Ottman R Tatemichi TK Tang MX Maestre G Ngai C Tycko B Ginsberg H The apolipoprotein epsilon 4 allele in patients with Alzheimer's disease Ann Neurol 1993 34 752 754 8239575 10.1002/ana.410340527 · DOI
  5. Schmechel DE Saunders AM Strittmatter WJ Crain BJ Hulette CM Joo SH Pericak-Vance MA Goldgaber D Roses AD Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease Proc Natl Acad Sci U S A 1993 90 9649 9653 8415756 10.1073/pnas.90.20.9649 PMC47627 · DOI · Paper page
  6. Greenberg SM Rebeck GW Vonsattel JP Gomez-Isla T Hyman BT Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy Ann Neurol 1995 38 254 259 7654074 10.1002/ana.410380219 · DOI
  7. Wisniewski T Ghiso J Frangione B Biology of A beta amyloid in Alzheimer's disease Neurobiol Dis 1997 4 313 328 9440120 10.1006/nbdi.1997.0147 · DOI
  8. Hardy J Selkoe DJ The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics Science 2002 297 353 356 12130773 10.1126/science.1072994 · DOI · Paper page
  9. Bales KR Verina T Cummins DJ Du Y Dodel RC Saura J Fishman CE DeLong CA Piccardo P Petegnief V Ghetti B Paul SM Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease Proc Natl Acad Sci U S A 1999 96 15233 15238 10611368 10.1073/pnas.96.26.15233 PMC24803 · DOI · Paper page
  10. Holtzman DM Fagan AM Mackey B Tenkova T Sartorius L Paul SM Bales K Ashe KH Irizarry MC Hyman BT Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model Ann Neurol 2000 47 739 747 10852539 10.1002/1531-8249(200006)47:6<739::AID-ANA6>3.0.CO;2-8 · DOI
  11. DeMattos RB Apolipoprotein E dose-dependent modulation of beta-amyloid deposition in a transgenic mouse model of Alzheimer's disease J Mol Neurosci 2004 23 255 262 15181254 10.1385/JMN:23:3:255 · DOI · Paper page
  12. Holtzman DM Bales KR Tenkova T Fagan AM Parsadanian M Sartorius LJ Mackey B Olney J McKeel D Wozniak D Paul SM Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease Proc Natl Acad Sci U S A 2000 97 2892 2897 10694577 10.1073/pnas.050004797 PMC16026 · DOI · Paper page
  13. Fagan AM Watson M Parsadanian M Bales KR Paul SM Holtzman DM Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease Neurobiol Dis 2002 9 305 318 11950276 10.1006/nbdi.2002.0483 · DOI · Paper page
  14. Artiga MJ Bullido MJ Frank A Sastre I Recuero M Garcia MA Lendon CL Han SW Morris JC Vazquez J Goate A Valdivieso F Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene Hum Mol Genet 1998 7 1887 1892 9811931 10.1093/hmg/7.12.1887 · DOI
  15. Bray NJ Jehu L Moskvina V Buxbaum JD Dracheva S Haroutunian V Williams J Buckland PR Owen MJ O'Donovan MC Allelic expression of APOE in human brain: effects of epsilon status and promoter haplotypes Hum Mol Genet 2004 13 2885 2892 15385439 10.1093/hmg/ddh299 · DOI · Paper page
  16. Blennow K Hesse C Fredman P Cerebrospinal fluid apolipoprotein E is reduced in Alzheimer's disease Neuroreport 1994 5 2534 2536 7696597 10.1097/00001756-199412000-00032 · DOI
  17. Lehtimaki T Pirttila T Mehta PD Wisniewski HM Frey H Nikkari T Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer's disease Hum Genet 1995 95 39 42 7814023 10.1007/BF00225071 · DOI · Paper page
  18. Landen M Hesse C Fredman P Regland B Wallin A Blennow K Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease and other forms of dementia is reduced but without any correlation to the apoE4 isoform Dementia 1996 7 273 278 8872419
  19. Mulder M Ravid R Swaab DF de Kloet ER Haasdijk ED Julk J van der Boom JJ Havekes LM Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinal fluid of Alzheimer disease patients are not related to apolipoprotein E4 Alzheimer Dis Assoc Disord 1998 12 198 203 9772023 10.1097/00002093-199809000-00012 · DOI
  20. Lefranc D Vermersch P Dallongeville J Daems-Monpeurt C Petit H Delacourte A Relevance of the quantification of apolipoprotein E in the cerebrospinal fluid in Alzheimer's disease Neurosci Lett 1996 212 91 94 8832646 10.1016/0304-3940(96)12774-9 · DOI · Paper page
  21. Lindh M Blomberg M Jensen M Basun H Lannfelt L Engvall B Scharnagel H Marz W Wahlund LO Cowburn RF Cerebrospinal fluid apolipoprotein E (apoE) levels in Alzheimer's disease patients are increased at follow up and show a correlation with levels of tau protein Neurosci Lett 1997 229 85 88 9223597 10.1016/S0304-3940(97)00429-1 · DOI
  22. Schiele F De Bacquer D Vincent-Viry M Beisiegel U Ehnholm C Evans A Kafatos A Martins MC Sans S Sass C Visvikis S De Backer G Siest G Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project Atherosclerosis 2000 152 475 488 10998477 10.1016/S0021-9150(99)00501-8 · DOI
  23. Wahrle SE Holtzman DM Differential metabolism of ApoE isoforms in plasma and CSF Exp Neurol 2003 183 4 6 12957482 10.1016/S0014-4886(03)00185-7 · DOI · Paper page
  24. Wahrle SE Jiang H Parsadanian M Legleiter J Han X Fryer JD Kowalewski T Holtzman DM ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE J Biol Chem 2004 279 40987 40993 15269217 10.1074/jbc.M407963200 · DOI · Paper page
  25. Hirsch-Reinshagen V Zhou S Burgess BL Bernier L McIsaac SA Chan JY Tansley GH Cohn JS Hayden MR Wellington CL Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain J Biol Chem 2004 279 41197 41207 15269218 10.1074/jbc.M407962200 · DOI · Paper page
  26. Koldamova R Staufenbiel M Lefterov I Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice J Biol Chem 2005 280 43224 43235 16207713 10.1074/jbc.M504513200 · DOI · Paper page
  27. Oram JF Molecular basis of cholesterol homeostasis: lessons from Tangier disease and ABCA1 Trends Mol Med 2002 8 168 173 11927274 10.1016/S1471-4914(02)02289-X · DOI
  28. Cohen JC Kiss RS Pertsemlidis A Marcel YL McPherson R Hobbs HH Multiple rare alleles contribute to low plasma levels of HDL cholesterol Science 2004 305 869 872 15297675 10.1126/science.1099870 · DOI · Paper page
  29. Frikke-Schmidt R Nordestgaard BG Jensen GB Tybjaerg-Hansen A Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population J Clin Invest 2004 114 1343 1353 15520867 10.1172/JCI200420361 PMC524222 · DOI
  30. Probst MC Thumann H Aslanidis C Langmann T Buechler C Patsch W Baralle FE Dallinga-Thie GM Geisel J Keller C Menys VC Schmitz G Screening for functional sequence variations and mutations in ABCA1 Atherosclerosis 2004 175 269 279 15262183 10.1016/j.atherosclerosis.2004.02.019 · DOI
  31. Clee SM Zwinderman AH Engert JC Zwarts KY Molhuizen HO Roomp K Jukema JW van Wijland M van Dam M Hudson TJ Brooks-Wilson A Genest J Jr. Kastelein JJ Hayden MR Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease Circulation 2001 103 1198 1205 11238261
  32. Wang J Burnett JR Near S Young K Zinman B Hanley AJ Connelly PW Harris SB Hegele RA Common and rare ABCA1 variants affecting plasma HDL cholesterol Arterioscler Thromb Vasc Biol 2000 20 1983 1989 10938021
  33. Wollmer MA Streffer JR Lutjohann D Tsolaki M Iakovidou V Hegi T Pasch T Jung HH Bergmann K Nitsch RM Hock C Papassotiropoulos A ABCA1 modulates CSF cholesterol levels and influences the age at onset of Alzheimer's disease Neurobiol Aging 2003 24 421 426 12600718 10.1016/S0197-4580(02)00094-5 · DOI
  34. Li Y Tacey K Doil L van Luchene R Garcia V Rowland C Schrodi S Leong D Lau K Catanese J Sninsky J Nowotny P Holmans P Hardy J Powell J Lovestone S Thal L Owen M Williams J Goate A Grupe A Association of ABCA1 with late-onset Alzheimer's disease is not observed in a case-control study Neurosci Lett 2004 366 268 271 15288432 10.1016/j.neulet.2004.05.047 · DOI
  35. Katzov H Chalmers K Palmgren J Andreasen N Johansson B Cairns NJ Gatz M Wilcock GK Love S Pedersen NL Brookes AJ Blennow K Kehoe PG Prince JA Genetic variants of ABCA1 modify Alzheimer disease risk and quantitative traits related to beta-amyloid metabolism Hum Mutat 2004 23 358 367 15024730 10.1002/humu.20012 · DOI
  36. Sundar PD Feingold E Minster RL Dekosky ST Kamboh MI Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease Neurobiol Aging 2006 16725228
  37. Pericak-Vance MA Grubber J Bailey LR Hedges D West S Santoro L Kemmerer B Hall JL Saunders AM Roses AD Small GW Scott WK Conneally PM Vance JM Haines JL Identification of novel genes in late-onset Alzheimer's disease Exp Gerontol 2000 35 1343 1352 11113612 10.1016/S0531-5565(00)00196-0 · DOI
  38. Myers A Wavrant De-Vrieze F Holmans P Hamshere M Crook R Compton D Marshall H Meyer D Shears S Booth J Ramic D Knowles H Morris JC Williams N Norton N Abraham R Kehoe P Williams H Rudrasingham V Rice F Giles P Tunstall N Jones L Lovestone S Williams J Owen MJ Hardy J Goate A Full genome screen for Alzheimer disease: stage II analysis Am J Med Genet 2002 114 235 244 11857588 10.1002/ajmg.10183 · DOI
  39. Blacker D Bertram L Saunders AJ Moscarillo TJ Albert MS Wiener H Perry RT Collins JS Harrell LE Go RC Mahoney A Beaty T Fallin MD Avramopoulos D Chase GA Folstein MF McInnis MG Bassett SS Doheny KJ Pugh EW Tanzi RE Results of a high-resolution genome screen of 437 Alzheimer's disease families Hum Mol Genet 2003 12 23 32 12490529 10.1093/hmg/ddg007 · DOI
  40. Scott WK Hauser ER Schmechel DE Welsh-Bohmer KA Small GW Roses AD Saunders AM Gilbert JR Vance JM Haines JL Pericak-Vance MA Ordered-subsets linkage analysis detects novel Alzheimer disease loci on chromosomes 2q34 and 15q22 Am J Hum Genet 2003 73 1041 1051 14564669 10.1086/379083 PMC1180484 · DOI
  41. Kehoe P Wavrant-De Vrieze F Crook R Wu WS Holmans P Fenton I Spurlock G Norton N Williams H Williams N Lovestone S Perez-Tur J Hutton M Chartier-Harlin MC Shears S Roehl K Booth J Van Voorst W Ramic D Williams J Goate A Hardy J Owen MJ A full genome scan for late onset Alzheimer's disease Hum Mol Genet 1999 8 237 245 9931331 10.1093/hmg/8.2.237 · DOI
  42. Fukumoto H Ingelsson M Garevik N Wahlund LO Nukina N Yaguchi Y Shibata M Hyman BT Rebeck GW Irizarry MC APOE epsilon 3/ epsilon 4 heterozygotes have an elevated proportion of apolipoprotein E4 in cerebrospinal fluid relative to plasma, independent of Alzheimer's disease diagnosis Exp Neurol 2003 183 249 253 12957508 10.1016/S0014-4886(03)00088-8 · DOI · Paper page
  43. Burns MP Vardanian L Pajoohesh-Ganji A Wang L Cooper M Harris DC Duff K Rebeck GW The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivo J Neurochem 2006 16771834
  44. Bateman RJ Wen G Morris JC Holtzman DM Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker Neurology 2007 68 666 669 17325273 10.1212/01.wnl.0000256043.50901.e3 · DOI · Paper page
  45. Schneider WJ Kovanen PT Brown MS Goldstein JL Utermann G Weber W Havel RJ Kotite L Kane JP Innerarity TL Mahley RW Familial dysbetalipoproteinemia. Abnormal binding of mutant apoprotein E to low density lipoprotein receptors of human fibroblasts and membranes from liver and adrenal of rats, rabbits, and cows J Clin Invest 1981 68 1075 1085 6270194 PMC370895
  46. Fryer JD Demattos RB McCormick LM O'Dell MA Spinner ML Bales KR Paul SM Sullivan PM Parsadanian M Bu G Holtzman DM The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice J Biol Chem 2005 280 25754 25759 15888448 10.1074/jbc.M502143200 · DOI · Paper page
  47. Nicoll JA Burnett C Love S Graham DI Dewar D Ironside JW Stewart J Vinters HV High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy Ann Neurol 1997 41 716 721 9189032 10.1002/ana.410410607 · DOI
  48. Chapman J Vinokurov S Achiron A Karussis DM Mitosek-Szewczyk K Birnbaum M Michaelson DM Korczyn AD APOE genotype is a major predictor of long-term progression of disability in MS Neurology 2001 56 312 316 11171894
  49. Friedman G Froom P Sazbon L Grinblatt I Shochina M Tsenter J Babaey S Yehuda B Groswasser Z Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury Neurology 1999 52 244 248 9932938
  50. Morris JC McKeel DW Jr. Fulling K Torack RM Berg L Validation of clinical diagnostic criteria for Alzheimer's disease Ann Neurol 1988 24 17 22 3415196 10.1002/ana.410240105 · DOI · Paper page
  51. Morris JC Storandt M McKeel DW Jr. Rubin EH Price JL Grant EA Berg L Cerebral amyloid deposition and diffuse plaques in "normal" aging: Evidence for presymptomatic and very mild Alzheimer's disease Neurology 1996 46 707 719 8618671
  52. Berg L McKeel DW Jr. Miller JP Storandt M Rubin EH Morris JC Baty J Coats M Norton J Goate AM Price JL Gearing M Mirra SS Saunders AM Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype Arch Neurol 1998 55 326 335 9520006 10.1001/archneur.55.3.326 · DOI · Paper page
  53. Krul ES Tikkanen MJ Schonfeld G Heterogeneity of apolipoprotein E epitope expression on human lipoproteins: importance for apolipoprotein E function J Lipid Res 1988 29 1309 1325 2466929
  54. Germer S Holland MJ Higuchi R High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR Genome Res 2000 10 258 266 10673283 10.1101/gr.10.2.258 PMC310828 · DOI

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Authors
Wahrle, S. E., Shah, A. R., Fagan, A. M., Smemo, S., Kauwe, J. S., Grupe, A., Hinrichs, A., Mayo, K., Jiang, H., Thal, L. J., Goate, A. M., & Holtzman, D. M.
Affiliations
  • Washington University in St. Louis (US)
  • University of California San Diego (US)
Corresponding author
Holtzman, David M
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2007-04-12
Volume
2
Issue
1
Pages
7-7
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-2-7
PMC
PMC1857699
OpenAlex
W2139564205
Cited by
84
References
3
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 10 · 2013: 5 · 2012: 10
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute on Aging (AG03991, AG 05681, P 50 AG05681, AG026276, P50AG005681, P01 AG0 3991, P01AG003991, R01AG016208, P01AG026276)
  • National Center for Research Resources (M01RR000036)
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 › Surgery › Lipoproteins and Cardiovascular Health
Keywords
apolipoprotein E, cerebrospinal fluid, ABCA1, Alzheimer's disease, amyloid-beta, APOE genotype, age-related variation, interindividual variability, lipid modification, genetic association, biomarker stability, cognitive aging

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