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Cited by 31Alzheimer's disease research and treatmentsIntracerebral and Subarachnoid Hemorrhage ResearchNeurological Disease Mechanisms and Treatments

Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study

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Marazuela, Paula, Paez-Montserrat, Berta, Bonaterra-Pastra, Anna, Solé, Montse, Hernández-Guillamon, Mar·2022·International Journal of Molecular Sciences
DOI 10.3390/ijms23094972PMC PMC9103818
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Abstract

The pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic.

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  1. [1]Weller R.O. Subash M. Preston S. Mazanti I. Carare R.O. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease Brain Pathol. 2008 18 253 266 10.1111/j.1750-3639.2008.00133.x 18363936 PMC8095597 · DOI
  2. [2]Hawkes C.A. Jayakody N. Johnston D.A. Bechmann I. Carare R.O. Failure of Perivascular Drainage of β-amyloid in Cerebral Amyloid Angiopathy Brain Pathol. 2014 24 396 403 10.1111/bpa.12159 24946077 PMC8029317 · DOI
  3. [3]Farid K. Charidimou A. Baron J.-C. Amyloid positron emission tomography in sporadic cerebral amyloid angiopathy: A systematic critical update NeuroImage: Clin. 2017 15 247 263 10.1016/j.nicl.2017.05.002 28560150 PMC5435601 · DOI
  4. [4]Winkler D.T. Bondolfi L. Herzig M.C. Jann L. Calhoun M.E. Wiederhold K.-H. Tolnay M. Staufenbiel M. Jucker M. Spontaneous Hemorrhagic Stroke in a Mouse Model of Cerebral Amyloid Angiopathy J. Neurosci. 2001 21 1619 1627 10.1523/JNEUROSCI.21-05-01619.2001 11222652 PMC6762950 · DOI
  5. [5]Sturchler-Pierrat C. Staufenbiel M. Pathogenic Mechanisms of Alzheimer’s Disease Analyzed in the APP23 Transgenic Mouse Model Ann. New York Acad. Sci. 2000 920 134 139 10.1111/j.1749-6632.2000.tb06915.x 11193142 · DOI
  6. [6]Myers A. Mcgonigle P. Overview of Transgenic Mouse Models for Alzheimer’s Disease Curr. Protoc. Neurosci. 2019 89 e81 10.1002/cpns.81 31532917 · DOI
  7. [7]Eede P. Obst J. Benke E. Yvon-Durocher G. Richard B.C. Gimber N. Schmoranzer J. Böddrich A. Wanker E.E. Prokop S. Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer’s disease-like mice EMBO Rep. 2020 21 e48530 10.15252/embr.201948530 32003148 PMC7054677 · DOI
  8. [9]Barnes L.L. Wilson R.S. Bienias J.L. Schneider J.A. Evans D.A. Bennett D.A. Sex Differences in the Clinical Manifestations of Alzheimer Disease Pathology Arch. Gen. Psychiatry 2005 62 685 691 10.1001/archpsyc.62.6.685 15939846 · DOI · Paper page
  9. [11]Nebel R.A. Aggarwal N.T. Barnes L.L. Gallagher A. Goldstein J.M. Kantarci K. Mallampalli M.P. Mormino E.C. Scott L. Yu W.H. Understanding the impact of sex and gender in Alzheimer’s disease: A call to action Alzheimer’s Dement. 2018 14 1171 1183 10.1016/j.jalz.2018.04.008 29907423 PMC6400070 · DOI · Paper page
  10. [12]Medeiros A.D.M. Silva R.H. Sex Differences in Alzheimer’s Disease: Where Do We Stand? J. Alzheimer’s Dis. 2019 67 35 60 10.3233/JAD-180213 30530972 · DOI
  11. [13]Fisher D.W. Bennett D.A. Dong H. Sexual dimorphism in predisposition to Alzheimer’s disease Neurobiol. Aging 2018 70 308 324 10.1016/j.neurobiolaging.2018.04.004 29754747 PMC6368179 · DOI · Paper page
  12. [14]Scheyer O. Rahman A. Hristov H. Berkowitz C. Isaacson R.S. Diaz Brinton R. Mosconi L. Female Sex and Alzheimer’s Risk: The Menopause Connection J. Prev. Alzheimers Dis. 2018 5 225 230 10.14283/jpad.2018.34 30298180 PMC6198681 · DOI · Paper page
  13. [15]Manson J.E. Aragaki A.K. Rossouw J.E. Anderson G.L. Prentice R.L. Lacroix A.Z. Chlebowski R.T. Howard B.V. Thomson C.A. Margolis K. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: The Women’s Health Initiative randomized trials JAMA—J. Am. Med. Assoc. 2017 318 927 938 10.1001/jama.2017.11217 28898378 PMC5728370 · DOI
  14. [16]Savolainen-Peltonen H. Rahkola-Soisalo P. Hoti F. Vattulainen P. Gissler M. Ylikorkala O. Mikkola T.S. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: Nationwide case-control study BMJ 2019 364 l665 10.1136/bmj.l665 30842086 PMC6402043 · DOI
  15. [17]Pike C.J. Carroll J.C. Rosario E.R. Barron A. Protective actions of sex steroid hormones in Alzheimer’s disease Front. Neuroendocr. 2009 30 239 258 10.1016/j.yfrne.2009.04.015 19427328 PMC2728624 · DOI
  16. [18]Rosario E.R. Carroll J. Pike C.J. Testosterone regulation of Alzheimer-like neuropathology in male 3xTg-AD mice involves both estrogen and androgen pathways Brain Res. 2010 1359 281 290 10.1016/j.brainres.2010.08.068 20807511 PMC2965035 · DOI
  17. [19]Lau C.-F. Ho Y.-S. Hung C.H.-L. Wuwongse S. Poon C.-H. Chiu K. Yang X. Chu L.-W. Chang R.C.-C. Protective Effects of Testosterone on Presynaptic Terminals against Oligomericβ-Amyloid Peptide in Primary Culture of Hippocampal Neurons BioMed Res. Int. 2014 2014 1 12 10.1155/2014/103906 PMC4086619 25045655 · DOI
  18. [20]Giannoni P. Arango-Lievano M. Das Neves I. Rousset M.-C. Baranger K. Rivera S. Jeanneteau F. Claeysen S. Marchi N. Cerebrovascular pathology during the progression of experimental Alzheimer’s disease Neurobiol. Dis. 2016 88 107 117 10.1016/j.nbd.2016.01.001 26774030 · DOI
  19. [21]Xu F. Kotarba A.E. Ou-Yang M.-H. Fu Z. Davis J. Smith S.O. Van Nostrand W.E. Early-onset Formation of Parenchymal Plaque Amyloid Abrogates Cerebral Microvascular Amyloid Accumulation in Transgenic Mice J. Biol. Chem. 2014 289 17895 17908 10.1074/jbc.M113.536565 24828504 PMC4067220 · DOI
  20. [22]Charidimou A. Imaizumi T. Moulin S. Biffi A. Samarasekera N. Yakushiji Y. Peeters A. Vandermeeren Y. Laloux P. Baron J.-C. Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds Neurology 2017 89 820 829 10.1212/WNL.0000000000004259 28747441 PMC5580863 · DOI
  21. [23]Reuter B. Venus A. Heiler P. Schad L. Ebert A. Hennerici M.G. Grudzenski S. Fatar M. Development of Cerebral Microbleeds in the APP23-Transgenic Mouse Model of Cerebral Amyloid Angiopathy—A 9.4 Tesla MRI Study Front. Aging Neurosci. 2016 8 170 10.3389/fnagi.2016.00170 27458375 PMC4937037 · DOI
  22. [24]Beckmann N. Doelemeyer A. Zurbruegg S. Bigot K. Theil D. Frieauff W. Kolly C. Moulin P. Neddermann D. Kreutzer R. Longitudinal noninvasive magnetic resonance imaging of brain microhemorrhages in BACE inhibitor–treated APP transgenic mice Neurobiol. Aging 2016 45 50 60 10.1016/j.neurobiolaging.2016.05.009 27459925 · DOI
  23. [25]Beckmann N. Schuler A. Mueggler T. Meyer E.P. Wiederhold K.-H. Staufenbiel M. Krucker T. Age-Dependent Cerebrovascular Abnormalities and Blood Flow Disturbances in APP23 Mice Modeling Alzheimer’s Disease J. Neurosci. 2003 23 8453 8459 10.1523/JNEUROSCI.23-24-08453.2003 13679413 PMC6740368 · DOI
  24. [27]Davis J. Xu F. Deane R. Romanov G. Previti M.L. Zeigler K. Zlokovic B.V. Van Nostrand W.E. Early-onset and Robust Cerebral Microvascular Accumulation of Amyloid β-Protein in Transgenic Mice Expressing Low Levels of a Vasculotropic Dutch/Iowa Mutant Form of Amyloid β-Protein Precursor J. Biol. Chem. 2004 279 20296 20306 10.1074/jbc.M312946200 14985348 · DOI · Paper page
  25. [28]Cacciottolo M. Christensen A. Moser A. Liu J. Pike C. Smith C. LaDu M.J. Sullivan P.M. Morgan T.E. Dolzhenko E. The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer’s disease of humans and mice Neurobiol. Aging 2015 37 47 57 10.1016/j.neurobiolaging.2015.10.010 26686669 PMC4687024 · DOI
  26. [29]Cacciottolo M. Morgan T.E. Finch C.E. Age, sex, and cerebral microbleeds in EFAD Alzheimer disease mice Neurobiol. Aging 2021 103 42 51 10.1016/j.neurobiolaging.2021.02.020 33813349 PMC8178216 · DOI
  27. [30]Greenberg S.M. Briggs M.E. Hyman B.T. Kokoris G.J. Takis C. Kanter D.S. Kase C.S. Pessin M.S. Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy Stroke 1996 27 1333 1337 10.1161/01.STR.27.8.1333 8711797 · DOI
  28. [32]Biffi A. Sonni A. Anderson C.D. Kissela B. Jagiella J.M. Schmidt H. Jimenez-Conde J. Bs B.M.H. Fernandez-Cadenas I. Msc L.C. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage Ann. Neurol. 2010 68 934 943 10.1002/ana.22134 21061402 PMC3058266 · DOI
  29. [33]Han B.H. Zhou M.L. Vellimana A.K. Milner E. Kim D.H. Greenberg J.K. Chu W. Mach R.H. Zipfel G.J. Resorufin analogs preferentially bind cerebrovascular amyloid: Potential use as imaging ligands for cerebral amyloid angiopathy Mol. Neurodegener. 2011 6 1 13 10.1186/1750-1326-6-86 22192811 PMC3259047 · DOI
  30. [34]Lane C.A. Hardy J. Schott J.M. Alzheimer’s disease Eur. J. Neurol. 2017 25 59 70 10.1111/ene.13439 28872215 · DOI · Paper page
  31. [36]Van Etten E.S. Gurol M.E. Van Der Grond J. Haan J. Viswanathan A. Schwab K.M. Ayres A.M. Algra A. Rosand J. Van Buchem M.A. Recurrent hemorrhage risk and mortality in hereditary and sporadic cerebral amyloid angiopathy Neurology 2016 87 1482 1487 10.1212/WNL.0000000000003181 27590282 PMC5075977 · DOI
  32. [37]Charidimou A. Boulouis G. Gurol M.E. Ayata C. Bacskai B.J. Frosch M.P. Viswanathan A. Greenberg S.M. Emerging concepts in sporadic cerebral amyloid angiopathy Brain 2017 140 1829 1850 10.1093/brain/awx047 28334869 PMC6059159 · DOI · Paper page
  33. [38]Charidimou A. Frosch M.P. Salman R.A.-S. Baron J.-C. Cordonnier C. Hernandez-Guillamon M. Linn J. Raposo N. Rodrigues M. Romero J.R. Advancing diagnostic criteria for sporadic cerebral amyloid angiopathy: Study protocol for a multicenter MRI-pathology validation of Boston criteria v2.0 Int. J. Stroke 2019 14 956 971 10.1177/1747493019855888 31514686 · DOI
  34. [39]Vinters H.V. Cerebral amyloid angiopathy. A critical review Stroke 1987 18 311 324 10.1161/01.STR.18.2.311 3551211 · DOI
  35. [40]Boulouis G. Charidimou A. Greenberg S.M. Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications Semin. Neurol. 2016 36 233 243 10.1055/s-0036-1581993 27214698 · DOI
  36. [41]Weller R.O. Preston S. Subash M. Carare R.O. Weller R.O. Preston S. Subash M. Carare R.O. Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease Alzheimer’s Res. Ther. 2009 1 6 10.1186/alzrt6 19822028 PMC2874258 · DOI
  37. [42]Keage H.A. Carare R.O. Friedland R.P. Ince P.G. Love S. A Nicoll J. Wharton S.B. Weller R.O. Brayne C. Population studies of sporadic cerebral amyloid angiopathy and dementia: A systematic review BMC Neurol. 2009 9 1 8 10.1186/1471-2377-9-3 19144113 PMC2647900 · DOI
  38. [43]Mielke M.M. Vemuri P. Rocca W.A. Clinical Epidemiology of Alzheimer’s Disease: Assessing Sex and Gender Differences Clin. Epidemiol. 2014 2014 37 48 10.2147/CLEP.S37929 24470773 PMC3891487 · DOI · Paper page
  39. [45]Mayeda E.R. Invited Commentary: Examining Sex/Gender Differences in Risk of Alzheimer Disease and Related Dementias—Challenges and Future Directions Am. J. Epidemiol. 2019 188 1224 1227 10.1093/aje/kwz047 30824902 PMC6601521 · DOI · Paper page
  40. [46]Allen N. Robinson A. Snowden J. Davidson Y.S. Mann D.M.A. Patterns of cerebral amyloid angiopathy define histopathological phenotypes in Alzheimer’s disease Neuropathol. Appl. Neurobiol. 2014 40 136 148 10.1111/nan.12070 23808763 · DOI
  41. [47]Jäkel L. De Kort A.M. Klijn C.J. Schreuder F.H. Verbeek M.M. Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis Alzheimers Dement. 2022 18 10 28 10.1002/alz.12366 34057813 PMC9290643 · DOI
  42. [48]O’Brien R.J. Wong P.C. Amyloid Precursor Protein Processing and Alzheimer’s Disease Annu. Rev. Neurosci. 2011 34 185 204 10.1146/annurev-neuro-061010-113613 21456963 PMC3174086 · DOI · Paper page
  43. [49]Zhang Y.-W. Thompson R. Zhang H. Xu H. APP processing in Alzheimer’s disease Mol. Brain 2011 4 3 10.1186/1756-6606-4-3 21214928 PMC3022812 · DOI · Paper page
  44. [50]Suzuki N. Iwatsubo T. Odaka A. Ishibashi Y. Kitada C. Ihara Y. High tissue content of soluble β1-40 is linked to cerebral amyloid angiopathy Am. J. Pathol. 1994 145 452 8053502 PMC1887395
  45. [51]Viswanathan A. Greenberg S.M. Cerebral amyloid angiopathy in the elderly Ann. Neurol. 2011 70 871 880 10.1002/ana.22516 22190361 PMC4004372 · DOI · Paper page
  46. [53]Howard R. Liu K.Y. Questions EMERGE as Biogen claims aducanumab turnaround Nat. Rev. Neurol. 2019 16 63 64 10.1038/s41582-019-0295-9 31784690 · DOI · Paper page
  47. [54]Sperling R.A. Jack C.R. Jr. Black S.E. Frosch M.P. Greenberg S.M. Hyman B.T. Scheltens P. Carrillo M.C. Thies W. Bednar M.M. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup Alzheimer’s Dement. 2011 7 367 385 10.1016/j.jalz.2011.05.2351 21784348 PMC3693547 · DOI · Paper page
  48. [56]DiFrancesco J.C. Longoni M. Piazza F. Anti-Aβ autoantibodies in amyloid related imaging abnormalities (ARIA): Candidate biomarker for immunotherapy in Alzheimer’s disease and cerebral amyloid angiopathy Front. Neurol. 2015 6 207 10.3389/fneur.2015.00207 26441825 PMC4585101 · DOI
  49. [57]Biffi A. Halpin A. Towfighi A. Gilson A. Busl K. Rost N. Smith E.E. Greenberg M.S. Rosand J. Viswanathan A. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy Neurology 2010 75 693 698 10.1212/WNL.0b013e3181eee40f 20733144 PMC2931649 · DOI
  50. [58]Weber S.A. Patel R.K. Lutsep H.L. Cerebral amyloid angiopathy: Diagnosis and potential therapies Expert Rev. Neurother. 2018 18 503 513 10.1080/14737175.2018.1480938 29792540 · DOI
  51. [59]Gatti L. Tinelli F. Scelzo E. Arioli F. Di Fede G. Obici L. Pantoni L. Giaccone G. Caroppo P. Parati E.A. Understanding the Pathophysiology of Cerebral Amyloid Angiopathy Int. J. Mol. Sci. 2020 21 3435 10.3390/ijms21103435 PMC7279405 32414028 · DOI
  52. [60]LaFerla F.M. Green K.N. Animal Models of Alzheimer Disease Cold Spring Harb. Perspect. Med. 2012 2 a006320 10.1101/cshperspect.a006320 23002015 PMC3543097 · DOI · Paper page
  53. [61]Jäkel L. Van Nostrand W.E. Nicoll J.A.R. Werring D.J. Verbeek M.M. Animal models of cerebral amyloid angiopathy Clin. Sci. 2017 131 2469 2488 10.1042/CS20170033 28963121 · DOI
  54. [62]Van Nostrand W.E. Melchor J.P. Romanov G. Zeigler K. Davis J. Pathogenic Effects of Cerebral Amyloid Angiopathy Mutations in the Amyloid β-Protein Precursor Ann. N. Y. Acad. Sci. 2002 977 258 265 10.1111/j.1749-6632.2002.tb04824.x 12480759 · DOI
  55. [63]Hendriks L. Van Duijn C.M. Cras P. Cruts M. Van Hul W. Van Harskamp F. Warren A. McInnis M.G. Antonarakis S. Martin J.-J. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein gene Nat. Genet. 1992 1 218 221 10.1038/ng0692-218 1303239 · DOI
  56. [64]Grabowski T.J. Cho H.S. Vonsattel J.P.G. Rebeck G.W. Greenberg S.M. Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy Ann. Neurol. 2001 49 697 705 10.1002/ana.1009 11409420 · DOI · Paper page
  57. [67]Kelly P. Bondolfi L. Hunziker D. Schlecht H.-P. Carver K. Maguire E. Abramowski D. Wiederhold K.-H. Sturchler-Pierrat C. Jucker M. Progressive age-related impairment of cognitive behavior in APP23 transgenic mice Neurobiol. Aging 2003 24 365 378 10.1016/S0197-4580(02)00098-2 12498971 · DOI
  58. [68]Giménez-Llort L. Marin-Pardo D. Marazuela P. Hernández-Guillamón M. Survival Bias and Crosstalk between Chronological and Behavioral Age: Age- and Genotype-Sensitivity Tests Define Behavioral Signatures in Middle-Aged, Old, and Long-Lived Mice with Normal and AD-Associated Aging Biomedicines 2021 9 636 10.3390/biomedicines9060636 34199476 PMC8228433 · DOI
  59. [70]Calhoun M.E. Burgermeister P. Phinney A.L. Stalder M. Tolnay M. Wiederhold K.-H. Abramowski D. Sturchler-Pierrat C. Sommer B. Staufenbiel M. Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid Proc. Natl. Acad. Sci. USA 1999 96 14088 14093 10.1073/pnas.96.24.14088 10570203 PMC24195 · DOI · Paper page
  60. [71]Wattendorff A.R. Frangione B. Luyendijk W. Bots G.T. Hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D): Clinicopathological studies J. Neurol. Neurosurg. Psychiatry 1995 58 699 705 10.1136/jnnp.58.6.699 7608669 PMC1073548 · DOI
  61. [74]Selkoe D.J. Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years EMBO Mol. Med. 2016 8 595 608 10.15252/emmm.201606210 27025652 PMC4888851 · DOI · Paper page
  62. [75]Tarasoff-Conway J.M. Carare R.O. Osorio R.S. Glodzik L. Butler T. Fieremans E. Axel L. Rusinek H. Nicholson C. Zlokovic B.V. Clearance systems in the brain-implications for Alzheimer disease Nat. Rev. Neurol. 2015 11 457 470 10.1038/nrneurol.2015.119 26195256 PMC4694579 · DOI · Paper page

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Authors
Marazuela, P., Paez-Montserrat, B., Bonaterra-Pastra, A., Solé, M., & Hernández-Guillamon, M.
Affiliations
  • Universitat Autònoma de Barcelona (ES)
  • Neurovascular Research Laboratory, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-04-29
Volume
23
Issue
9
Pages
4972
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms23094972
PMC
PMC9103818
OpenAlex
W4225114874
Cited by
31
References
13
Citations by year
2026: 5 · 2025: 9 · 2024: 9 · 2023: 8
FWCI
4.02
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Instituto de Salud Carlos III (ISCIII) (PI20/00465, RD21/0006/0007)
  • European Regional Development Fund (FEDER) (PI20/00465, RD21/0006/0007)
  • The Neurovascular Research Laboratory (PI20/00465, RD21/0006/0007)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
cerebral amyloid angiopathy, APP23 mice, 5xFAD mice, amyloid-beta deposition, cerebral microbleeds, sex differences, Alzheimer's disease, vascular dysfunction, neuritic plaques, transgenic mouse model
MeSH terms
Alzheimer Disease, Amyloidosis, Animals, Brain, Disease Models, Animal, Female, Mice, Transgenic, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Mice, Plaque, Amyloid

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