CoChat
Sign Up
Cited by 66Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Apolipoprotein B is a novel marker for early tau pathology in Alzheimer's disease

Open access
Picard, Cynthia, Nilsson, Nathalie, Labonté, Anne, Auld, Daniel, Rosa‐Neto, Pedro, the Alzheimer's Disease Neuroimaging Initiative, Ashton, Nicholas J., Zetterberg, Henrik +5 more·2022·Alzheimer's & Dementia
DOI 10.1002/alz.12442PMC PMC9293308
Open this paper in CoChat — free accountOpen PDF

Abstract

Introduction: We examine the role of brain apolipoprotein B (apoB) as a putative marker of early tau pathology and cognitive decline. Methods: Cerebrospinal fluid (CSF) samples from cognitively normal and Alzheimer's disease (AD) participants were collected to measure protein levels of apoB and AD biomarkers amyloid beta (Aβ), t‐tau and p‐tau, as well as synaptic markers GAP43, SYNAPTOTAGMIN‐1, synaptosome associated protein 25 (SNAP‐25), and NEUROGRANIN. CSF apoB levels were contrasted with positron emission tomography (PET) scan measures of Aβ (18F‐NAV4694) and Tau (flortaucipir) along with cognitive assessment alterations over 6 to 8 years. Results: CSF apoB levels were elevated in AD participants and correlated with t‐tau, p‐tau, and the four synaptic markers in pre‐symptomatic individuals. In the latter, CSF apoB levels correlated with PET flortaucipir‐binding in entorhinal, parahippocampal, and fusiform regions. Baseline CSF apoB levels were associated with longitudinal visuospatial cognitive decline. Discussion: CSF apoB markedly associates with early tau dysregulation in asymptomatic subjects and identifies at‐risk individuals predisposed to develop visuospatial cognitive decline over time.

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 · 10.1002/alz.12442

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

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?

  • Cerebrospinal fluid apoB levels are correlated with tau pathology in pre-symptomatic individuals and elevated in AD patients.

    “a recent study has demonstrated that cerebrospinal fluid apoB levels are correlated with tau pathology in pre-symptomatic individuals and elevated in AD patients [11]”

    From Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants (2023) · cites this paper as [11]

Self-check

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

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

Cites

Flagged first, then by citations

Research works printed but not linked: 46

  1. [1]Hofman A, Ott A, Breteler MM, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet. 1997; 349(9046): 151‐ 154. 9111537
  2. [2]Marchant NL, Reed BR, Sanossian N, et al. The aging brain and cognition: contribution of vascular injury and abeta to mild cognitive dysfunction. JAMA Neurol. 2013; 70(4): 488‐ 495. 23400560 PMC3771392
  3. [3]Power MC, Rawlings A, Sharrett AR, et al. Association of midlife lipids with 20‐year cognitive change: a cohort study. Alzheimers Dement. 2018; 14(2): 167‐ 177. 28916238 PMC5803364
  4. [5]Wingo TS, Cutler DJ, Wingo AP, et al. Association of early‐onset Alzheimer disease with elevated low‐density lipoprotein cholesterol levels and rare genetic coding variants of APOB association of early‐onset AD with elevated LDL‐C levels and rare APOB coding variants association of early‐onset AD with elevated LDL‐C levels and rare APOB coding variants. JAMA Neurol. 2019; 76(7): 809‐ 817. 31135820 PMC6547122
  5. [6]Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 1993; 342(8873): 697‐ 699. 8103819
  6. [8]Sparks DL, Martin TA, Gross DR. Link between heart disease, cholesterol, and Alzheimer's disease: a review. Microsc Res Tech. 2000; 50(4): 287‐ 290. 10936882
  7. [9]Caramelli P, Nitrini R, Maranhao R, et al. Increased apolipoprotein B serum concentration in Alzheimer's disease. Acta Neurologica Scandinavica. 1999; 100(1): 61‐ 63. 10416513
  8. [10]Kuo YM, Emmerling MR, Bisgaier CL, et al. Elevated low‐density lipoprotein in Alzheimer's disease correlates with brain abeta 1‐42 levels. Biochem Biophys Res Commun. 1998; 252(3): 711‐ 715. 9837771
  9. [11]Löffler T, Flunkert S, Havas D, et al. Impact of ApoB‐100 expression on cognition and brain pathology in wild‐type and hAPPsl mice. Neurobiol Aging. 2013; 34(10): 2379‐ 2388. 23643485
  10. [12]Breitner JCS, Poirier J, Etienne PE, Leoutsakos JM, PREVENT‐AD Research G. Rationale and structure for a new center for studies on prevention of Alzheimer's disease (StoP‐AD). J Prev Alz Dis. 2016; 3(4): 236‐ 242. 29199324
  11. [13]Lleo A, Alcolea D, Martinez‐Lage P, et al. Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study. Alzheimers Dement. 2019; 15(6): 742‐ 753. 30967340
  12. [14]Brinkmalm A, Brinkmalm G, Honer WG, et al. SNAP‐25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease. Mol Neurodegener. 2014; 9(1): 53. 25418885 PMC4253625
  13. [16]Portelius E, Olsson B, Höglund K, et al. Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology. Acta Neuropathol. 2018; 136(3): 363‐ 376. 29700597 PMC6096740
  14. [17]Sandelius Å, Portelius E, Källén Å, et al. Elevated CSF GAP‐43 is Alzheimer's disease specific and associated with tau and amyloid pathology. Alzheimer's Dement. 2019; 15(1): 55‐ 64. 30321501 PMC6333489
  15. [18]McSweeney M, Pichet Binette A, Meyer PF, et al. Intermediate flortaucipir uptake is associated with Abeta‐PET and CSF tau in asymptomatic adults. Neurology. 2020; 94(11): e1190‐ e1200. 32015176
  16. [19]Ossenkoppele R, Rabinovici GD, Smith R, et al. Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2018; 320(11): 1151‐ 1162. 30326496 PMC6233630
  17. [20]Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998; 20(3): 310‐ 319. 9845158
  18. [21]Chertkow H, Borrie M, Whitehead V, et al. The comprehensive assessment of neurodegeneration and dementia: canadian cohort study. Can J Neurol Sci. 2019; 46(5): 499‐ 511. 31309917
  19. [22]Kennedy JJ, Abbatiello SE, Kim K, et al. Demonstrating the feasibility of large‐scale development of standardized assays to quantify human proteins. Nat Methods. 2014; 11(2): 149‐ 155. 24317253 PMC3922286
  20. [23]Purcell S, Neale B, Todd‐Brown K, et al. PLINK: a tool set for whole‐genome association and population‐based linkage analyses. Am J Hum Genet. 2007; 81(3): 559‐ 575. 17701901 PMC1950838
  21. [24]Shabalin AA. Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics. 2012; 28(10): 1353‐ 1358. 22492648 PMC3348564
  22. [25]Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population‐based study. Lancet Neurol. 2006; 5(9): 735‐ 741. 16914401
  23. [27]Takahashi H, Lassmann T, Murata M, Carninci P. 5' end‐centered expression profiling using cap‐analysis gene expression and next‐generation sequencing. Nat Protoc. 2012; 7(3): 542‐ 561. 22362160 PMC4094379
  24. [28]Lein ES, Hawrylycz MJ, Ao N, et al. Genome‐wide atlas of gene expression in the adult mouse brain. Nature. 2007; 445(7124): 168‐ 176. 17151600
  25. [29]Kunkle BW, Grenier‐Boley B, Sims R, et al. Genetic meta‐analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 2019; 51(3): 414‐ 430. 30820047 PMC6463297
  26. [30]Beecham GW, Hamilton K, Naj AC, et al. Genome‐wide association meta‐analysis of neuropathologic features of Alzheimer's disease and related dementias. PLoS Genet. 2014; 10(9): e1004606. 25188341 PMC4154667
  27. [31]Picard C, Julien C, Frappier J, et al. Alterations in cholesterol metabolism‐related genes in sporadic Alzheimer's disease. Neurobiol Aging. 2018; 66: 180. e1‐ e9. 29503034
  28. [32]Bellenguez C, Küçükali F, Jansen I, et al. New insights on the genetic etiology of Alzheimer's and related dementia. medRxiv. 2020; 2020. 10.01.20200659.
  29. [33]Csont T, Bereczki E, Bencsik P, et al. Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB‐100 transgenic mice. Cardiovasc Res. 2007; 76(1): 100‐ 109. 17658498
  30. [34]Lénárt N, Szegedi V, Juhász G, et al. Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB‐100 transgenic mice. PLoS One. 2012; 7(9): e46007. 23029362 PMC3454377
  31. [35]Algotsson A, Winblad B. The integrity of the blood‐brain barrier in Alzheimer's disease. Acta Neurol Scand. 2007; 115(6): 403‐ 408. 17511849
  32. [37]Leduc V, Jasmin‐Belanger S, Poirier J. APOE and cholesterol homeostasis in Alzheimer's disease. Trends Mol Med. 2010; 16(10): 469‐ 477. 20817608
  33. [38]Terrisse L, Seguin D, Bertrand P, Poirier J, Milne R, Rassart E. Modulation of apolipoprotein D and apolipoprotein E expression in rat hippocampus after entorhinal cortex lesion. Mol Brain Res. 1999; 70(1): 26‐ 35. 10381540
  34. [39]Poirier J, Baccichet A, Dea D, Gauthier S. Cholesterol‐synthesis and lipoprotein reuptake during synaptic remodeling in hippocampus in adult‐rats. Neuroscience. 1993; 55(1): 81‐ 90. 8350994
  35. [40]May PC, Johnson SA, Poirier J, Lampertetchells M, Finch CE. Altered gene‐expression in Alzheimers‐disease brain‐tissue. Can J Neurol Sci. 1989; 16(4): 473‐ 476. 2680007
  36. [41]Mauch DH, Nagler K, Schumacher S, et al. CNS synaptogenesis promoted by glia‐derived cholesterol. Science. 2001; 294(5545): 1354‐ 1357. 11701931
  37. [42]Beffert U, Stolt PC, Herz J. Functions of lipoprotein receptors in neurons. J Lipid Res. 2004; 45(3): 403‐ 409. 14657206
  38. [43]Kester MI, Teunissen CE, Crimmins DL, et al. Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer disease. JAMA Neurol. 2015; 72(11): 1275‐ 1280. 26366630 PMC4694558
  39. [44]Poirier J. Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease. Trends Neurosci. 1994; 17(12): 525‐ 530. 7532337
  40. [45]Poirier J. Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer's disease. Neurobiol Aging. 2005; 26(3): 355‐ 361. 15639314
  41. [47]Morizawa YM, Hirayama Y, Ohno N, et al. Reactive astrocytes function as phagocytes after brain ischemia via ABCA1‐mediated pathway. Nat Commun. 2017; 8(1): 28. 28642575 PMC5481424
  42. [49]Mauch DH, Nägler K, Schumacher S, et al. CNS synaptogenesis promoted by glia‐derived cholesterol. Science. 2001; 294(5545): 1354‐ 1357. 11701931
  43. [50]Poirier J, Miron J, Picard C, et al. Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease. Neurobiol Aging. 2014; 35(Suppl 2): S3‐ S10. 24973118 PMC5140289
  44. [51]Jasmin SB, Pearson V, Lalonde D, Domenger D, Theroux L, Poirier J. Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver‐X receptor agonist treatment. Brain Res. 2014; 1562: 39‐ 51. 24661912 PMC5138061
  45. [52]Arendt T. Disturbance of neuronal plasticity is a critical pathogenetic event in Alzheimer's disease. Int J Dev Neurosci. 2001; 19(3): 231‐ 245. 11337192
  46. [53]Arendt T, Schindler C, Bruckner MK, et al. Plastic neuronal remodeling is impaired in patients with Alzheimer's disease carrying apolipoprotein epsilon 4 allele. J Neurosci. 1997; 17(2): 516‐ 529. 8987775 PMC6573225

Cited by

Sorted by citations

Authors
Picard, C., Nilsson, N., Labonté, A., Auld, D., Rosa‐Neto, P., Initiative, T. A. D. N., Ashton, N. J., Zetterberg, H., Blennow, K., Breitner, J. C. B., Villeneuve, S., Poirier, J., & for the PREVENT‐AD research group
Affiliations
  • Douglas Mental Health University Institute (CA)
  • McGill University (CA)
  • Sahlgrenska University Hospital (SE)
  • Douglas Mental Health University Institute Montréal Québec Canada
Corresponding author
Poirier, Judes
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2021-09-29
Volume
18
Issue
5
Pages
875-887
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.12442
PMC
PMC9293308
OpenAlex
W3202870961
Cited by
66
References
7
Citations by year
2026: 11 · 2025: 10 · 2024: 22 · 2023: 14 · 2022: 7 · 2021: 2
FWCI
7.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institutes of Health (5u01ag024904-10)
  • Canadian Institutes of Health Research (153287_1)
  • National Institute on Aging (U01-AG-024904)
Topics
  • Health Sciences › Medicine › Physiology › 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 B, Alzheimer's disease
MeSH terms
Alzheimer Disease, Apolipoproteins, Apolipoproteins B, Humans, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Apolipoprotein B-100, Cognitive Dysfunction

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