CoChat
Sign Up
Cited by 13Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory

Open access
Biundo, Fabrizio, Ishiwari, Keita, Del Prete, Dolores, D’Adamio, Luciano·2015·Neurobiology of Learning and Memory
DOI 10.1016/j.nlm.2015.10.009PMC PMC4900468
Open this paper in CoChat — free accountOpen PDF

Abstract

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers.

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 · 10.1016/j.nlm.2015.10.009

Cites

11 of 11 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?

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: 55

  1. Bachmeier C Shackleton B Ojo J Paris D Mullan M Crawford F 2014 Apolipoprotein E isoform-specific effects on lipoprotein receptor processing NeuroMolecular Medicine 16 686 696 25015123 PMC4280344
  2. Baxter LC Caselli RJ Johnson SC Reiman E Osborne D 2003 Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer’s disease Neurobiology of Aging 24 947 952 12928055
  3. Beffert U Danik M Krzywkowski P Ramassamy C Berrada F Poirier J 1998 The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer’s disease Brain Research Brain Research Reviews 27 119 142 9622609
  4. Bell RD Sagare AP Friedman AE Bedi GS Holtzman DM Deane R Zlokovic BV 2007 Transport pathways for clearance of human Alzheimer’s amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system Journal of Cerebral Blood Flow and Metabolism 27 909 918 17077814 PMC2853021
  5. Bondi MW Salmon DP Monsch AU Galasko D Butters N Klauber MR Saitoh T 1995 Episodic memory changes are associated with the APOEepsilon 4 allele in nondemented older adults Neurology 45 2203 2206 8848194
  6. Bosco P Gueant-Rodriguez RM Anello G Spada RS Romano A Caraci F Gueant JL 2005 Allele epsilon 4 of APOE is a stronger predictor of Alzheimer risk in Sicily than in continental South Italy Neuroscience Letters 388 168 172 16040191
  7. Bour A Grootendorst J Vogel E Kelche C Dodart JC Bales K Mathis C 2008 Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks Behavioural Brain Research 193 174 182 18572260
  8. Boyles JK Pitas RE Wilson E Mahley RW Taylor JM 1985 Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system The Journal of Clinical Investigation 76 1501 1513 3932467 PMC424114
  9. Corder EH Saunders AM Risch NJ Strittmatter WJ Schmechel DE Gaskell PC Jr Pericak-Vance MA 1994 Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease Nature Genetics 7 180 184 7920638
  10. Corder EH Saunders AM Strittmatter WJ Schmechel DE Gaskell PC Small GW Pericak-Vance MA 1993 Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families Science (New York, NY) 261 921 923 8346443
  11. Crean S Ward A Mercaldi CJ Collins JM Cook MN Baker NL Arrighi HM 2011 Apolipoprotein E epsilon4 prevalence in Alzheimer’s disease patients varies across global populations: A systematic literature review and metaanalysis Dementia and Geriatric Cognitive Disorders 31 20 30 21124030
  12. Flory JD Manuck SB Ferrell RE Ryan CM Muldoon MF 2000 Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults American Journal of Medical Genetics 96 707 711 11121165
  13. Frieden C Garai K 2012 Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease Proceedings of the National academy of Sciences of the United States of America 109 8913 8918 22615372 PMC3384159
  14. Ghiso J Rostagno A Tomidokoro Y Lashley T Bojsen-Moller M Braendgaard H Frangione B 2006 Genetic alterations of the BRI2 gene: Familial British and Danish dementias Brain Pathology 16 71 79 16612984 PMC8095812
  15. Giliberto L Matsuda S Vidal R D’Adamio L 2009 Generation and initial characterization of FDD knock in mice PLoS One 4 e7900 19924302 PMC2774945
  16. Grootendorst J Bour A Vogel E Kelche C Sullivan PM Dodart JC Mathis C 2005 Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior Behavioural Brain Research 159 1 14 15794991
  17. Hardy J 1997 Amyloid, the presenilins and Alzheimer’s disease Trends in Neurosciences 20 154 159 9106355
  18. Hauser PS Narayanaswami V Ryan RO 2011 Apolipoprotein E: From lipid transport to neurobiology Progress in Lipid Research 50 62 74 20854843 PMC3022415
  19. Holton JL Lashley T Ghiso J Braendgaard H Vidal R Guerin CJ Revesz T 2002 Familial Danish dementia: A novel form of cerebral amyloidosis associated with deposition of both amyloid-Dan and amyloid-beta Journal of Neuropathology and Experimental Neurology 61 254 267 11895040
  20. Huang Y 2011 Roles of apolipoprotein E4 (ApoE4) in the pathogenesis of Alzheimer’s disease: Lessons from ApoE mouse models Biochemical Society Transactions 39 924 932 21787325
  21. Knouff C Hinsdale ME Mezdour H Altenburg MK Watanabe M Quarfordt SH Maeda N 1999 Apo E structure determines VLDL clearance and atherosclerosis risk in mice The Journal of Clinical Investigation 103 1579 1586 10359567 PMC408371
  22. Mahley RW 1988 Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology Science (New York, NY) 240 622 630 3283935
  23. Matsuda S Giliberto L Matsuda Y Davies P McGowan E Pickford F D’Adamio L 2005 The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production The Journal of Biological Chemistry 280 28912 28916 15983050
  24. Matsuda S Giliberto L Matsuda Y McGowan EM D’Adamio L 2008 BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 28 8668 8676 18753367 PMC3844774
  25. Matsuda S Matsuda Y Snapp EL D’Adamio L 2011 Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles Neurobiology of Aging 32 1400 1408 19748705 PMC2932834
  26. Matsuda S Tamayev R D’Adamio L 2011 Increased AbetaPP processing in familial Danish dementia patients Journal of Alzheimer’s Disease: JAD 27 385 391 21841249 PMC3690758
  27. Nalbantoglu J Tirado-Santiago G Lahsaini A Poirier J Goncalves O Verge G Shapiro ML 1997 Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein Nature 387 500 505 9168112
  28. Oster-Granite ML McPhie DL Greenan J Neve RL 1996 Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein Journal of Neuroscience 16 6732 6741 8824314 PMC6579256
  29. Panza F Solfrizzi V Torres F Mastroianni F Colacicco AM Basile AM Capurso A 2000 Apolipoprotein E in Southern Italy: Protective effect of epsilon 2 allele in early- and late-onset sporadic Alzheimer’s disease Neuroscience Letters 292 79 82 10998553
  30. Panza F Solfrizzi V Torres F Mastroianni F Del Parigi A Colacicco AM Capurso A 1999 Decreased frequency of apolipoprotein E epsilon4 allele from Northern to Southern Europe in Alzheimer’s disease patients and centenarians Neuroscience Letters 277 53 56 10643896
  31. Pfrieger FW 2003 Cholesterol homeostasis and function in neurons of the central nervous system Cellular and Molecular Life Sciences 60 1158 1171 12861382 PMC11138592
  32. Pitas RE Boyles JK Lee SH Hui D Weisgraber KH 1987 Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B, E(LDL) receptors in the brain The Journal of Biological Chemistry 262 14352 14360 3115992
  33. Plant GT Revesz T Barnard RO Harding AE Gautier-Smith PC 1990 Familial cerebral amyloid angiopathy with nonneuritic amyloid plaque formation Brain 113 Pt 3 721 747 2364266
  34. Revesz T Holton JL Doshi B Anderton BH Scaravilli F Plant GT 1999 Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation Acta Neuropathologica 97 170 176 9928828
  35. Rostagno A Revesz T Lashley T Tomidokoro Y Magnotti L Braendgaard H Ghiso J 2002 Complement activation in chromosome 13 dementias. Similarities with Alzheimer’s disease The Journal of Biological Chemistry 277 49782 49790 12388551
  36. Saunders AM Strittmatter WJ Schmechel D George-Hyslop PH Pericak-Vance MA Joo SH Roses AD 1993 Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease Neurology 43 1467 1472 8350998
  37. Selkoe DJ 1991 The molecular pathology of Alzheimer’s disease Neuron 6 487 498 1673054
  38. Selkoe DJ 2002 Deciphering the genesis and fate of amyloid beta-protein yields novel therapies for Alzheimer disease The Journal of Clinical Investigation 110 1375 1381 12438432 PMC151820
  39. Selkoe DJ 2011 Alzheimer’s disease Cold Spring Harbor Perspectives in Biology 3 PMC3119915 21576255
  40. Sherrington R Rogaev EI Liang Y Rogaeva EA Levesque G Ikeda M St George-Hyslop PH 1995 Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease Nature 375 754 760 7596406
  41. Stromgren E Dalby A Dalby MA Ranheim B 1970 Cataract, deafness, cerebellar ataxia, psychosis and dementia – A new syndrome Acta Neurologica Scandinavica 46 Suppl 43 261 5457846
  42. Suh YH Kim HS Lee JP Park CH Jeong SJ Kim SS Kim SS 2000 Roles of A beta and carboxyl terminal peptide fragments of amyloid precursor protein in Alzheimer disease Journal of Neural Transmission. Supplementum 65 82 11128614
  43. Sullivan PM Mace BE Maeda N Schmechel DE 2004 Marked regional differences of brain human apolipoprotein E expression in targeted replacement mice Neuroscience 124 725 733 15026113
  44. Tamayev R D’Adamio L 2012 Inhibition of gamma-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia Molecular Neurodegeneration 7 19 22537414 PMC3407505
  45. Tamayev R Giliberto L Li W d’Abramo C Arancio O Vidal R D’Adamio L 2010 Memory deficits due to familial British dementia BRI2 mutation are caused by loss of BRI2 function rather than amyloidosis The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 30 14915 14924 21048150 PMC3056548
  46. Tamayev R Matsuda S Arancio O D’Adamio L 2012 Beta-but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia EMBO Molecular Medicine 4 171 179 22170863 PMC3376850
  47. Tamayev R Matsuda S Fa M Arancio O D’Adamio L 2010 Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits Proceedings of the National academy of Sciences of the United States of America 107 20822 20827 21098268 PMC2996452
  48. Tamayev R Matsuda S Giliberto L Arancio O D’Adamio L 2011 APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant The EMBO Journal 30 2501 2509 21587206 PMC3116289
  49. Tang MX Maestre G Tsai WY Liu XH Feng L Chung WY Mayeux R 1996 Effect of age, ethnicity, and head injury on the association between APOE genotypes and Alzheimer’s disease Annals of the New York Academy of Sciences 802 6 15 8993479
  50. Tang MX Stern Y Marder K Bell K Gurland B Lantigua R Mayeux R 1998 The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics JAMA 279 751 755 9508150
  51. Vidal R Frangione B Rostagno A Mead S Revesz T Plant G Ghiso J 1999 A stop-codon mutation in the BRI gene associated with familial British dementia Nature 399 776 781 10391242
  52. Weisgraber KH Rall SC Jr Mahley RW 1981 Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms The Journal of Biological Chemistry 256 9077 9083 7263700
  53. West HL Rebeck GW Hyman BT 1994 Frequency of the apolipoprotein E epsilon 2 allele is diminished in sporadic Alzheimer disease Neuroscience Letters 175 46 48 7970208
  54. Wilson RS Schneider JA Barnes LL Beckett LA Aggarwal NT Cochran EJ Bennett DA 2002 The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period Archives of Neurology 59 1154 1160 12117364
  55. Worster-Drought C Hill TR McMenemey WH 1933 Familial presenile dementia with spastic paralysis Journal of Neurology and Psychopathology 14 27 34 21610757 PMC1038860

Cited by

Sorted by citations

Authors
Biundo, F., Ishiwari, K., Del Prete, D., & D’Adamio, L.
Affiliations
Albert Einstein College of Medicine (US)
ORCID
Venue
Neurobiology of Learning and Memory
Publisher
Elsevier BV
Published
2015-12
Volume
126
Pages
18-30
ISSN
1074-7427 (ISSN-L)
DOI
10.1016/j.nlm.2015.10.009
PMC
PMC4900468
OpenAlex
W1961804775
Cited by
13
References
11
Citations by year
2026: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2019: 1 · 2018: 2 · 2017: 2
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Learning and Memory (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Alzheimer's Association (R01AG033007, ZEN-11-201425)
  • Glaucoma Research Foundation
  • Edward N. and Della L. Thome Memorial Foundation
  • National Institutes of Health (ZEN-11-201425)
  • National Institute on Aging (R01AG022024, R01AG033007, R01AG041531, R21AG048971)
  • National Institute of Neurological Disorders and Stroke (T32NS007098)
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
APOE ε4, APOE3, familial Danish dementia, Alzheimer's disease, learning and memory, spatial working memory, short-term memory, long-term memory, APP processing, genetic interactions, targeted replacement mice, knock-in mice
MeSH terms
Alzheimer Disease, Animals, Cataract, Cerebellar Ataxia, Deafness, Dementia, Humans, Learning, Male, Membrane Proteins, Memory, Short-Term, Mice, Inbred C57BL, Mutation, Protein Isoforms, Adaptor Proteins, Signal Transducing, Mice, Apolipoprotein E3, Apolipoprotein E4, Spatial Memory

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