CoChat
Sign Up
Cited by 27

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease

Turri, Marta, Conti, Elisa, Pavanello, Chiara, Gastoldi, Francesco, Palumbo, Marcella, Bernini, Franco, Aprea, Vittoria, Re, Francesca, Barbiroli, Alberto, Emide, Davide, Galimberti, Daniela, Tremolizzo, Lucio, Zimetti, Francesca, Calabresi, Laura, AGAINST-AD Group, Andreoni, Simona, Appollonio, Ildebrando, Da Re, Fulvio, Ferrarese, Carlo, Karantzoulis, Aristotelis, Negro, Giulia, Pozzi, Federico Emanuele, Remoli, Giulia, Storti, Benedetta, Zoia, Chiara Paola·2023·Alzheimer's Research & Therapy
DOI 10.1186/s13195-023-01241-6PMC PMC10199596
Open this paper in CoChat — free account

Abstract

Objective: The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients. Methods: The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF. Results: AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ 1-42 CSF content. Conclusion: Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ 1-42).

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s13195-023-01241-6

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 40

  1. Turri M, Marchi C, Adorni MP, Calabresi L, Zimetti F. Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders. Biochim Biophys Acta Mol Cell Biol Lipids. 2022;1867(5):159123. · DOI · Paper page
  2. Kontush A, Lindahl M, Lhomme M, Calabresi L, Chapman MJ, Davidson WS. Structure of HDL: particle subclasses and molecular components. Handb Exp Pharmacol. 2015;224:3–51. · DOI
  3. Jonas A. Lecithin cholesterol acyltransferase. Biochim Biophys Acta. 2000;1529(1–3):245–56. · DOI
  4. Husain MA, Laurent B, Plourde M. APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics. Front Neurosci. 2021;15:630502. · DOI · Paper page
  5. Nguyen D, Dhanasekaran P, Nickel M, Nakatani R, Saito H, Phillips MC, et al. Molecular basis for the differences in lipid and lipoprotein binding properties of human apolipoproteins E3 and E4. Biochemistry. 2010;49(51):10881–9. · DOI · Paper page
  6. Li H, Dhanasekaran P, Alexander ET, Rader DJ, Phillips MC, Lund-Katz S. Molecular mechanisms responsible for the differential effects of apoE3 and apoE4 on plasma lipoprotein-cholesterol levels. Arterioscler Thromb Vasc Biol. 2013;33(4):687–93. · DOI
  7. Frisoni GB, Calabresi L, Geroldi C, Bianchetti A, D’Acquarica AL, Govoni S, et al. Apolipoprotein E epsilon 4 allele in Alzheimer’s disease and vascular dementia. Dementia. 1994;5(5):240–2.
  8. Dal Magro R, Simonelli S, Cox A, Formicola B, Corti R, Cassina V, et al. The Extent of Human Apolipoprotein A-I Lipidation Strongly Affects the beta-Amyloid Efflux Across the Blood-Brain Barrier in vitro. Front Neurosci. 2019;13:419. · DOI
  9. Fernández-de-Retana S, Cano-Sarabia M, Marazuela P, Sánchez-Quesada JL, Garcia-Leon A, Montañola A, et al. Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral beta-amyloidosis. Sci Rep. 2017;7(1):14637. · DOI
  10. Vance JE, Hayashi H. Formation and function of apolipoprotein E-containing lipoproteins in the nervous system. Biochim Biophys Acta. 2010;1801(8):806–18. · DOI · Paper page
  11. Marchi C, Adorni MP, Caffarra P, Ronda N, Spallazzi M, Barocco F, et al. ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer’s disease. J Lipid Res. 2019;60(8):1449–56. · DOI · Paper page
  12. Yassine HN, Feng Q, Chiang J, Petrosspour LM, Fonteh AN, Chui HC, et al. ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer’s Disease. J Am Heart Assoc. 2016;5(2):e002886. · DOI · Paper page
  13. Ko YA, Billheimer JT, Lyssenko NN, Kueider-Paisley A, Wolk DA, Arnold SE, et al. ApoJ/Clusterin concentrations are determinants of cerebrospinal fluid cholesterol efflux capacity and reduced levels are associated with Alzheimer’s disease. Alzheimers Res Ther. 2022;14(1):194. · DOI
  14. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–9. · DOI · Paper page
  15. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87(5):539–47. · DOI · Paper page
  16. Conti E, Nacinovich R, Bomba M, Raggi ME, Neri F, Ferrarese C, et al. Beta-amyloid plasma levels in adolescents with anorexia nervosa of the restrictive type. Neuropsychobiology. 2015;71(3):154–7. · DOI
  17. Arcaro M, Fenoglio C, Serpente M, Arighi A, Fumagalli GG, Sacchi L, et al. A Novel Automated Chemiluminescence Method for Detecting Cerebrospinal Fluid Amyloid-Beta 1–42 and 1–40, Total Tau and Phosphorylated-Tau: Implications for Improving Diagnostic Performance in Alzheimer’s Disease. Biomedicines. 2022;10(10):2667. · DOI
  18. Calabresi L, Pisciotta L, Costantin A, Frigerio I, Eberini I, Alessandrini P, et al. The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families. Arterioscler Thromb Vasc Biol. 2005;25(9):1972–8. · DOI
  19. Asztalos BF, de la Llera-Moya M, Dallal GE, Horvath KV, Schaefer EJ, Rothblat GH. Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux. J Lipid Res. 2005;46(10):2246–53. · DOI
  20. Zimetti F, Weibel GK, Duong M, Rothblat GH. Measurement of cholesterol bidirectional flux between cells and lipoproteins. J Lipid Res. 2006;47(3):605–13. · DOI
  21. Palumbo M, Giammanco A, Purrello F, Pavanello C, Mombelli G, Di Pino A, et al. Effects of PCSK9 inhibitors on HDL cholesterol efflux and serum cholesterol loading capacity in familial hypercholesterolemia subjects: a multi-lipid-center real-world evaluation. Front Mol Biosci. 2022;9:925587. · DOI
  22. Favari E, Zimetti F, Bortnick AE, Adorni MP, Zanotti I, Canavesi M, et al. Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages. FEBS Lett. 2005;579(29):6537–42. · DOI · Paper page
  23. Gelissen IC, Harris M, Rye KA, Quinn C, Brown AJ, Kockx M, et al. ABCA1 and ABCG1 synergize to mediate cholesterol export to apoA-I. Arterioscler Thromb Vasc Biol. 2006;26(3):534–40. · DOI
  24. Frisoni GB, Calabresi L, Geroldi C, Bianchetti A, D’Acquarica AL, Govoni S, et al. Apolipoprotein E epsilon 4 allele frequency in vascular dementia and Alzheimer’s disease. Stroke. 1994;25(8):1703–4. · DOI
  25. Frisoni GB, Govoni S, Geroldi C, Bianchetti A, Calabresi L, Franceschini G, et al. Gene dose of the epsilon 4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer’s disease. Ann Neurol. 1995;37(5):596–604. · DOI · Paper page
  26. Endo Y, Fujita M, Ikewaki K. HDL Functions-Current Status and Future Perspectives. Biomolecules. 2023;13(1):105. · DOI
  27. Bjorkhem I, Leoni V, Meaney S. Genetic connections between neurological disorders and cholesterol metabolism. J Lipid Res. 2010;51(9):2489–503. · DOI
  28. Pavanello C, Calabresi L. Genetic, biochemical, and clinical features of LCAT deficiency: update for 2020. Curr Opin Lipidol. 2020;31(4):232–7. · DOI
  29. Pavanello C, Ossoli A, Strazzella A, Risè P, Veglia F, Lhomme M, et al. Plasma FA composition in familial LCAT deficiency indicates SOAT2-derived cholesteryl ester formation in humans. J Lipid Res. 2022;63(7):100232. · DOI
  30. Adorni MP, Ronda N, Bernini F, Zimetti F. High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives. Cells. 2021;10(3):574. · DOI
  31. Rye KA, Bright R, Psaltis M, Barter PJ. Regulation of reconstituted high density lipoprotein structure and remodeling by apolipoprotein E. J Lipid Res. 2006;47(5):1025–36. · DOI · Paper page
  32. Lennol MP, Sánchez-Domínguez I, Cuchillo-Ibañez I, Camporesi E, Brinkmalm G, Alcolea D, et al. Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer’s disease patients. Alzheimers Res Ther. 2022;14(1):161. · DOI
  33. Varesi A, Carrara A, Pires VG, Floris V, Pierella E, Savioli G, et al. Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview. Cells. 2022;11(8):1367. · DOI
  34. Hawksworth J, Fernández E, Gevaert K. A new generation of AD biomarkers: 2019 to 2021. Ageing Res Rev. 2022;79:101654. · DOI
  35. Wang J, Zhang X, Zhu B, Fu P, On the behalf of Alzheimer’s Disease Neuroimaging Initiative. Association of Clusterin Levels in Cerebrospinal Fluid with Synaptic Degeneration Across the Alzheimer’s Disease Continuum. Neuropsychiatr Dis Treat. 2020;16:183–90. · DOI
  36. Minta K, Brinkmalm G, Janelidze S, Sjödin S, Portelius E, Stomrud E, et al. Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases. Alzheimers Res Ther. 2020;12(1):19. · DOI
  37. Johansson P, Almqvist EG, Bjerke M, Wallin A, Johansson JO, Andreasson U, et al. Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer’s Disease. J Alzheimers Dis. 2017;59(3):1017–26. · DOI
  38. Sodero AO. 24S-hydroxycholesterol: Cellular effects and variations in brain diseases. J Neurochem. 2021;157(4):899–918. · DOI
  39. Schönknecht P, Lütjohann D, Pantel J, Bardenheuer H, Hartmann T, von Bergmann K, et al. Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer’s disease compared to healthy controls. Neurosci Lett. 2002;324(1):83–5. · DOI
  40. Zuliani G, Donnorso MP, Bosi C, Passaro A, Dalla Nora E, Zurlo A, et al. Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer’s disease or vascular dementia: a case-control study. BMC Neurol. 2011;11:121. · DOI

Cited by

Sorted by citations

Metadata

Authors
Turri, M., Conti, E., Pavanello, C., Gastoldi, F., Palumbo, M., Bernini, F., Aprea, V., Re, F., Barbiroli, A., Emide, D., Galimberti, D., Tremolizzo, L., Zimetti, F., Calabresi, L., AGAINST-AD Group, Andreoni, S., Appollonio, I., Da Re, F., Ferrarese, C., Karantzoulis, A., Negro, G., Pozzi, F. E., Remoli, G., Storti, B., & Zoia, C. P.
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2023-05-20
Volume
15
Issue
1
ISSN
1758-9193
DOI
10.1186/s13195-023-01241-6
PMC
PMC10199596
Cited by
27
References
6
Language
en
Licence
Funders
  • Ministero dell'Università e della Ricerca (MNESYS (PE0000006), PRIN2017PFYK27)
  • Università degli Studi di Milano

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review