Patterns and severity of vascular amyloid in Alzheimer’s disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer’s disease
Open accessAbstract
In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD ( APP dup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer’s disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vascular disease, we additionally aimed to explore the role of APOE genotype in CAA severity and subtypes. Plaque formation was greater in DS and missense APP mutations than in APP dup, sEOAD and sLOAD cases. Conversely, CAA was more severe in APP dup and missense APP mutations, and in DS, compared to sEOAD and sLOAD. When stratified by CAA subtype from 1 to 4, there were no differences in plaque scores between the groups, though in patients with APP dup, APP mutations and sEOAD, types 2 and 3 CAA were more common than type 1. Conversely, in DS, sLOAD and controls, type 1 CAA was more common than types 2 and 3. APOE ε4 allele frequency was greater in sEOAD and sLOAD compared to APP dup, missense APP mutations, DS and controls, and varied between each of the CAA phenotypes with APOE ε4 homozygosity being more commonly associated with type 3 CAA than types 1 and 2 CAA in sLOAD and sEOAD. The differing patterns in CAA within individuals of each group could be a reflection of variations in the efficiency of perivascular drainage, this being less effective in types 2 and 3 CAA leading to a greater burden of CAA in parenchymal arteries and capillaries. Alternatively, as suggested by immunostaining using carboxy-terminal specific antibodies, it may relate to the relative tissue burdens of the two major forms of Aβ, with higher levels of Aβ 40 promoting a more ‘aggressive’ form of CAA, and higher levels of Aβ 42(3) favouring a greater plaque burden. Possession of APOE ε4 allele, especially ε4 homozygosity, favours development of CAA generally, and as type 3 particularly, in sEOAD and sLOAD.
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Capillary CAA is linked to APOE4 and a variant (C766T (rs1799986)) in LRP-1, suggesting capillary CAA may represent a subtype of AD.
“Capillary CAA is also linked to APOE4 and a variant (C766T (rs1799986)) in the LDL receptor related protein 1 (LRP-1), a receptor for apolipoproteins, which suggests that capillary CAA my also represent a subtype of AD [105, 106].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [106]
The Results (Effect of APOE genotype; page unavailable) report that APOE ε4 homozygosity was more common in type 3 CAA, a phenotype involving capillaries. The Discussion (page unavailable) cautions that APOE genotype did not greatly influence CAA phenotype overall. The paper does not establish the claimed link to LRP-1 C766T (rs1799986) or suggest that capillary CAA is a subtype of AD. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPeople with DSAD have a significant burden of cerebral amyloid angiopathy (CAA), with more severe CAA found than in sporadic AD.
“People with DSAD have a significant burden of cerebral amyloid angiopathy (CAA), with more severe CAA found than in sporadic AD [25, 40].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [40]
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Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490 · see citing works
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · see citing works
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Self-citationRovelet‐Lecrux, A., Hannequin, D., Raux, G., Meur, N. L., Laquerrière, A., Vital, A., Dumanchin‐Njock, C., Feuillette, S., Brice, A., Vercelletto, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1718 · Cited by 1,249 · see citing works
Self-citationHuman ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,227 · cited 1× · see citing works
“Nonetheless, it is known that an increase in ε4 allele copy from 0 to 2 is associated with higher levels of Aβ40 deposition (as plaques) in sLOAD [13, 27], possession of ε4 allele/ApoE E4 isoform decreases brain clearance of Aβ [7], and ApoE E4 isoform promotes fibrillogenesis [23].”
BackgroundApolipoprotein E genotyping by one-stage PCR
Wenham, P. R., Price, W. H., & Blundell, G. (1991) · The Lancet · doi:10.1016/0140-6736(91)92823-k · Cited by 1,070 · see citing works
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
Snowden, J. S., Rollinson, S., Thompson, J. C., Harris, J. M., Stopford, C. L., Richardson, A. M. T., Jones, M., Gerhard, A., Davidson, Y. S., Robinson, A., et al. (2012) · Brain · doi:10.1093/brain/awr355 · Cited by 523 · see citing works
Self-citationMolecular mapping of alzheimer‐type dementia in Down's syndrome
Prasher, V. P., Farrer, M. J., Kessling, A. M., Fisher, E. M. C., West, R. J., Barber, P. C., & Butler, A. C. (1998) · Annals of Neurology · doi:10.1002/ana.410430316 · Cited by 414 · see citing works
Self-citationSleegers, K., Brouwers, N., Gijselinck, I., Theuns, J., Goossens, D., Wauters, J., Del‐Favero, J., Cruts, M., van Duijn, C. M., & Broeckhoven, C. V. (2006) · Brain · doi:10.1093/brain/awl203 · Cited by 406 · see citing works
Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome
Iwatsubo, T., Mann, D. M. A., Odaka, A., Suzuki, N., & Ihara, Y. (1995) · Annals of Neurology · doi:10.1002/ana.410370305 · Cited by 380 · see citing works
Self-citationPhenotype associated with APP duplication in five families
Cabrejo, L., Guyant‐Maréchal, L., Laquerrière, A., Vercelletto, M., Fournière, F. D. L., Thomas-Antérion, C., Verny, C., Letournel, F., Pasquier, F., Vital, A., et al. (2006) · Brain · doi:10.1093/brain/awl237 · Cited by 342 · see citing works
Self-citationWeller, R. O., Boche, D., & Nicoll, J. A. R. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0498-z · Cited by 297 · see citing works
Thompson, J. C. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.033779 · Cited by 251 · see citing works
Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer’s Disease: The Role of APP
Doran, E., Keator, D., Head, E., Phelan, M. J., Kim, R., Totoiu, M., Barrio, J. R., Small, G. W., Potkin, S. G., & Lott, I. T. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160836 · Cited by 244 · see citing works
Snowden, J. S., Thompson, J. C., Stopford, C. L., Richardson, A. M. T., Gerhard, A., Neary, D., & Mann, D. M. A. (2011) · Brain · doi:10.1093/brain/awr189 · Cited by 238 · see citing works
Self-citationKim, S., Sato, Y., Mohan, P. S., Peterhoff, C. M., Pensalfini, A., Rigoglioso, A., Jiang, Y., & Nixon, R. A. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.97 · Cited by 220 · see citing works
Olichney, J. M., Hansen, L. A., Galasko, D., Saitoh, T., Hofstetter, C. R., Katzman, R., & Thal, L. J. (1996) · Neurology · doi:10.1212/wnl.47.1.190 · Cited by 216 · see citing works
Alzheimer disease and Down syndrome: factors in pathogenesis
Lott, I. T., & Head, E. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.08.005 · Cited by 212 · see citing works
High tissue content of soluble beta 1-40 is linked to cerebral amyloid angiopathy.
Suzuki, N., Iwatsubo, T., Odaka, A., Ishibashi, Y., Kitada, C., & Ihara, Y. (1994) · PubMed Central · Cited by 206 · see citing works
Self-citationMann, D. M. A., Iwatsubo, T., Ihara, Y., Cairns, N. J., Lantos, P. L., Bogdanović, N., Lannfelt, L., Winblad, B. G., Maat–Schieman, M. L. C., & Rossor, M. N. (1996) · Europe PMC (PubMed Central) · Cited by 184 · see citing works
Self-citationMann, D. M. A., Pickering-Brown, S. M., Takeuchi, A., & Iwatsubo, T. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64688-3 · Cited by 182 · see citing works
Self-citationColacurcio, D. J., Pensalfini, A., Jiang, Y., & Nixon, R. A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.001 · Cited by 167 · see citing works
Risk of Major Cardiovascular Events in People with Down Syndrome
Sobey, C. G., Judkins, C. P., Sundararajan, V., Phan, T. G., Drummond, G. R., & Srikanth, V. K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137093 · Cited by 156 · see citing works
Alexander, M., Petri, H., Ding, Y., Wandel, C., Khwaja, O., & Foskett, N. (2015) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.12868 · Cited by 138 · see citing works
Rabbitt, P., McInnes, L., Diggle, P. J., Holland, F., Bent, N., Abson, V., Pendleton, N., & Horan, M. A. (2004) · Aging Neuropsychology and Cognition · doi:10.1080/13825580490511116 · Cited by 130 · see citing works
Self-citationImpact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer’s disease
Shinohara, M., Murray, M. E., Frank, R. D., Shinohara, M., DeTure, M., Yamazaki, Y., Tachibana, M., Atagi, Y., Davis, M. D., Liu, C.-C., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1580-y · Cited by 123 · see citing works
Aβ‐peptide length aid apolipoprotein E genotype in Alzheimer's disease
Gearing, M., Mori, H., & Mirra, S. S. (1996) · Annals of Neurology · doi:10.1002/ana.410390320 · Cited by 120 · see citing works
Davidson, Y. S., Barker, H., Robinson, A., Thompson, J. C., Harris, J., Troakes, C., Smith, B. N., Al‐Saraj, S., Shaw, C. E., Rollinson, S. J., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-70 · Cited by 115 · see citing works
Self-citationCerebrovascular pathology in Down syndrome and Alzheimer disease
Head, E., Phelan, M. J., Doran, E., Kim, R. C., Poon, W. W., Schmitt, F. A., & Lott, I. T. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0499-4 · Cited by 105 · see citing works
Thal, D. R., Papassotiropoulos, A., Saido, T. C., Griffin, W. S. T., Mrak, R. E., Kölsch, H., Tredici, K. D., Attems, J., & Ghebremedhin, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0707-9 · Cited by 103 · see citing works
Cossec, J., Lavaur, J., Berman, D. E., Rivals, I., Hoischen, A., Stora, S., Ripoll, C., Mircher, C., Grattau, Y., Olivo‐Marín, J., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds142 · Cited by 100 · see citing works
Self-citationKasuga, K., Shimohata, T., Nishimura, A., Shiga, A., Mizuguchi, T., Tokunaga, J., Ohno, T., Miyashita, A., Kuwano, R., Matsumoto, N., et al. (2009) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2008.161703 · Cited by 97 · see citing works
APP locus duplication in a Finnish family with dementia and intracerebral haemorrhage
Rovelet‐Lecrux, A., Frébourg, T., Tuominen, H. J., Majamaa, K., Campion, D., & Remes, A. M. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.113514 · Cited by 95 · see citing works
The Site of the Earliest Lesions of Alzheimer's Disease
Mann, D. M., & Esiri, M. M. (1988) · New England Journal of Medicine · doi:10.1056/nejm198803243181218 · Cited by 94 · see citing works
Self-citationMcNaughton, D., Knight, W. D., Guerreiro, R. J., Ryan, N. S., Lowe, J., Poulter, M., Nicholl, D. J., Hardy, J., Révész, T., Lowe, J. S., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.10.010 · Cited by 93 · see citing works
Mann, D. M. A., Iwatsubo, T., Pickering-Brown, S. M., Owen, F., Saido, T. C., & Perry, R. H. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(96)13294-8 · Cited by 91 · see citing works
Self-citationClinical aspects and biomarkers of Alzheimer's disease in Down syndrome
Zis, P., & Strydom, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.08.024 · Cited by 88 · see citing works
Self-citationINTRAFAMILIAL DIVERSITY OF PHENOTYPE ASSOCIATED WITH APP DUPLICATION
Guyant-Marechal, I., Berger, É., Laquerrière, A., Rovelet‐Lecrux, A., Viennet, G., Frébourg, T., Rumbach, L., Campion, D., & Hannequin, D. (2008) · Neurology · doi:10.1212/01.wnl.0000339400.64213.56 · Cited by 64 · see citing works
Self-citationPatterns of cerebral amyloid angiopathy define histopathological phenotypes in A lzheimer's disease
Allen, N., Robinson, A., Snowden, J. S., Davidson, Y. S., & Mann, D. M. A. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12070 · Cited by 49 · see citing works
Self-citationIntracerebral haemorrhage in Down syndrome: protected or predisposed?
Buss, L., Fisher, E., Hardy, J., Nižetić, D., Groet, J., Pulford, L. J., & Strydom, A. (2016) · F1000Research · doi:10.12688/f1000research.7819.1 · Cited by 48 · see citing works
Self-citationMann, D. M. A., Takeuchi, A., Sato, S., Cairns, N. J., Lantos, P. L., Rossor, M. N., Haltia, M., Kalimo, H., & Iwatsubo, T. (2001) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2001.00316.x · Cited by 42 · see citing works
Self-citationMutation in the 3’untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy
Nicolas, G., Wallon, D., Goupil, C., Richard, A., Pottier, C. P., Dorval, V., Sarov-Rivière, M., Riant, F., Hervé, D., Amouyel, P., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.61 · Cited by 35 · see citing works
Blom, E. S., Viswanathan, J., Kilander, L., Helisalmi, S., Soininen, H. S., Lannfelt, L., Ingelsson, M., Glaser, A., & Hiltunen, M. O. (2007) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201966 · Cited by 34 · see citing works
Thonberg, H., Fallström, M., Björkström, J., Schoumans, J., Nennesmo, I., & Graff, C. (2011) · BMC Research Notes · doi:10.1186/1756-0500-4-476 · Cited by 33 · see citing works
Large APP locus duplication in a sporadic case of cerebral haemorrhage
Lladó, A., Grau‐Rivera, O., Sánchez‐Valle, R., Balasa, M., Obach, V., Amaro, S., Rey, M. J., Molinuevo, J. L., Gelpí, E., & Antonell, A. (2014) · Neurogenetics · doi:10.1007/s10048-014-0395-z · Cited by 19 · see citing works
Domingues‐Montanari, S., Parés, M., Hernández‐Guillamón, M., Fernández‐Cadenas, I., Mendióroz, M., Ortega, G., Boada, M., Masjuán, J., Huertas, N., Álvarez‐Sabín, J., et al. (2011) · European Journal of Neurology · doi:10.1111/j.1468-1331.2011.03401.x · Cited by 10 · see citing works
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The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329 · see citing works
“Capillary CAA is also linked to APOE4 and a variant (C766T (rs1799986)) in the LDL receptor related protein 1 (LRP-1), a receptor for apolipoproteins, which suggests that capillary CAA my also represent a subtype of AD [105, 106].”
BackgroundKent, S. A., Spires-Jones, T. L., & Durrant, C. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02196-w · Cited by 446 · see citing works
Alzheimer's disease associated with Down syndrome: a genetic form of dementia
Fortea, J., Zaman, S. H., Hartley, S., Rafii, M. S., Head, E., & Carmona-Iragui, M. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00245-3 · Cited by 357 · see citing works
The amyloid plaque proteome in early onset Alzheimer’s disease and Down syndrome
Drummond, E., Kavanagh, T., Pires, G., Marta-Ariza, M., Kanshin, E., Nayak, S., Faustin, A., Berdah, V., Ueberheide, B., & Wisniewski, T. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01356-1 · Cited by 137 · see citing works
Davidson, Y. S., Robinson, A., Prasher, V. P., & Mann, D. M. A. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0559-4 · Cited by 141 · see citing works
Self-citationMicroglial activation states and their implications for Alzheimer's Disease
Valiukas, Z., Tangalakis, K., Apostolopoulos, V., & Feehan, J. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2024.100013 · Cited by 155 · see citing works
Alić, I., Goh, P. A., Murray, A., Portelius, E., Gkanatsiou, E., Gough, G., Mok, K. Y., Koschut, D., Brunmeir, R., Yeap, Y. J., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0806-5 · Cited by 123 · see citing works
Self-citationFurther understanding the connection between Alzheimer's disease and Down syndrome
Snyder, H. M., Bain, L. J., Brickman, A. M., Carrillo, M. C., Esbensen, A. J., Espinosa, J. M., Fernandez, F., Fortea, J., Hartley, S. L., Head, E., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12112 · Cited by 105 · see citing works
Self-citationUnderstanding the Pathophysiology of Cerebral Amyloid Angiopathy
Gatti, L., Tinelli, F., Scelzo, E., Arioli, F., Fede, G. D., Obici, L. P., Pantoni, L., Giaccone, G., Caroppo, P., Parati, E. A., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103435 · Cited by 91 · see citing works
Plasma biomarkers for amyloid, tau, and cytokines in Down syndrome and sporadic Alzheimer’s disease
Startin, C. M., Ashton, N. J., Hamburg, S., Hithersay, R., Wiseman, F. K., Mok, K. Y., Hardy, J., Lleó, A., Lovestone, S., Parnetti, L., et al. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0477-0 · Cited by 85 · see citing works
Self-citationExploring cerebral amyloid angiopathy: Insights into pathogenesis, diagnosis, and treatment
Cozza, M., Amadori, L., & Boccardi, V. (2023) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2023.120866 · Cited by 84 · see citing works
Carmona‐Iragui, M., Videla, L., Lleó, A., & Fortea, J. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22709 · Cited by 64 · see citing works
The amyloid precursor protein: a converging point in Alzheimer’s disease
Delport, A., & Hewer, R. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02863-x · Cited by 62 · see citing works
Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease
Kalaria, R. N., & Falla, D. S. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.07.004 · Cited by 55 · see citing works
Clinical considerations in early-onset cerebral amyloid angiopathy
Banerjee, G., Collinge, J., Fox, N. C., Lashley, T., Mead, S., Schott, J. M., Werring, D. J., & Ryan, N. S. (2023) · Brain · doi:10.1093/brain/awad193 · Cited by 54 · see citing works
Caballero, M. Á. A., Song, Z., Rubinski, A., Duering, M., Dichgans, M., Park, D. C., & Ewers, M. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12062 · Cited by 51 · see citing works
Cryo-EM structures of amyloid-β and tau filaments in Down syndrome
Fernández, A., Hoq, M. R., Hallinan, G. I., Li, D., Bharath, S. R., Vago, F. S., Zhang, X., Ozcan, K. A., Newell, K. L., Garringer, H. J., et al. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01252-3 · Cited by 50 · see citing works
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Self-citationRéthelyi, J., Vincze, K., Schall, D., Glennon, J. C., & Berkel, S. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105330 · Cited by 49 · see citing works
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Abrahamson, E. E., Head, E., Lott, I. T., Handen, B. L., Mufson, E. J., Christian, B. T., Klunk, W. E., & Ikonomović, M. D. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22713 · Cited by 45 · see citing works
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Grangeon, L., Cassinari, K., Rousseau, S., Croisile, B., Formaglio, M., Moreaud, O., Boutonnât, J., Meur, N. L., Miné, M., Coste, T., et al. (2021) · Neurology Genetics · doi:10.1212/nxg.0000000000000609 · Cited by 38 · see citing works
Rujeedawa, T., Félez, E. C., Clare, I. C. H., Fortea, J., Strydom, A., Rebillat, A., Coppus, A. M. W., Levin, J., & Zaman, S. H. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10194582 · Cited by 40 · see citing works
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Johannesson, M., Sahlin, C., Söderberg, L., Basun, H., Fälting, J. M., Möller, C., Zachrisson, O., Sunnemark, D., Svensson, A., Odergren, T., et al. (2021) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2021.103641 · Cited by 32 · see citing works
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Chen, J., Chen, J.-S., Li, S., Zhang, F., Deng, J., Zeng, L., & Tan, J. (2023) · Aging and Disease · doi:10.14336/ad.2023.0308 · Cited by 30 · see citing works
Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease
Joseph‐Mathurin, N., Wang, G., Kantarci, K., Jack, C. R., McDade, E., Hassenstab, J. J., Blazey, T., Gordon, B. A., Su, Y., Chen, G., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000011542 · Cited by 28 · see citing works
Martini, A. C., Gross, T. J., Head, E., & Mapstone, M. E. (2022) · Neuron · doi:10.1016/j.neuron.2022.04.001 · Cited by 26 · see citing works
Plasma amyloid and tau as dementia biomarkers in Down syndrome: Systematic review and meta‐analyses
Alhajraf, F., Ness, D., Hye, A., & Strydom, A. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22715 · Cited by 26 · see citing works
Self-citationHithersay, R., Baksh, R. A., Startin, C. M., Wijeratne, P. A., Hamburg, S., Carter, B., & Strydom, A. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12222 · Cited by 25 · see citing works
Self-citationPatterns of Mixed Pathologies in Down Syndrome
Ichimata, S., Yoshida, K., Visanji, N. P., Lang, A. E., Nishida, N., & Kovacs, G. G. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215675 · Cited by 25 · see citing works
Lloyd, G. M., Trejo‐Lopez, J. A., Xia, Y., McFarland, K. N., Lincoln, S., Ertekin‐Taner, N., Giasson, B. I., Yachnis, A. T., & Prokop, S. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-0891-3 · Cited by 23 · see citing works
Bi, J., Lai, H., Wang, P., Sui, H., Li, X., & Bai, L. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.295349 · Cited by 23 · see citing works
Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches
Farrell, C., Mumford, P., & Wiseman, F. K. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.909669 · Cited by 22 · see citing works
Phenotype and imaging features associated with APP duplications
Grangeon, L., Charbonnier, C., Zaréa, A., Rousseau, S., Rovelet‐Lecrux, A., Bendetowicz, D., Lemaitre, M., Malrain, C., Quillard‐Muraine, M., Cassinari, K., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01172-2 · Cited by 18 · see citing works
Self-citationCell models for Down syndrome-Alzheimer’s disease research
Wu, Y., West, N. R., Bhattacharyya, A., & Wiseman, F. K. (2022) · Neuronal Signaling · doi:10.1042/ns20210054 · Cited by 17 · see citing works
Ichimata, S., Martínez-Valbuena, I., Lee, S., Li, J., Karakani, A. M., & Kovács, G. G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411596 · Cited by 15 · see citing works
Mgaieth, F., Baksh, R. A., Startin, C. M., Hamburg, S., Hithersay, R., Pape, S. E., Zetterberg, H., Ashton, N. J., Tamayo‐Elizalde, M., Saini, F., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13097 · Cited by 13 · see citing works
Self-citationKasri, A., Camporesi, E., Gkanatsiou, E., Boluda, S., Brinkmalm, G., Stimmer, L., Ge, J., Hanrieder, J., Villain, N., Duyckaerts, C. J., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02756-4 · Cited by 15 · see citing works
Self-citationDierssen, M., Hérault, Y., Helguera, P. R., de Lagrán, M. M., Vázquez, A. V., Christian, B. T., Carmona‐Iragui, M., Wiseman, F. K., Mobley, W. C., Fisher, E., et al. (2021) · Molecular Syndromology · doi:10.1159/000514437 · Cited by 11 · see citing works
Self-citationMolecular neuroimaging in dominantly inherited versus sporadic early-onset Alzheimer’s disease
Iaccarino, L., Llibre‐Guerra, J. J., McDade, E., Edwards, L., Gordon, B. A., Benzinger, T. L. S., Hassenstab, J. J., Kramer, J. H., Li, Y., Miller, B. L., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae159 · Cited by 10 · see citing works
Farrell, C., Buhidma, Y., Mumford, P., Heywood, W. E., Hällqvist, J., Flores-Aguilar, L., Andrews, E. J., Rahimzadah, N., Taso, O. S., Doran, E., et al. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02889-0 · Cited by 9 · see citing works
“We also found that in DSAD cases, APOE also stains leptomeningeal and parenchymal vessel structures, which may reflect antibody binding to the amyloid found in the vessels due to CAA, which has a high occurrence in DSAD [25, 26, 36, 40], or staining of vascular cells.”
Li, Y., Zhang, J., Ma, B., Yu, W., Xu, M., Luan, W., Yu, Q., Zhang, L., Rong, R., Fu, Y., et al. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.124786 · Cited by 9 · see citing works
Exposure to the Heavy-Metal Lead Induces DNA Copy Number Alterations in Zebrafish Cells
Lee, J., & Freeman, J. L. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00156 · Cited by 9 · see citing works
Cerebral Aβ deposition in an Aβ-precursor protein-transgenic rhesus monkey
Chan, A. W. S., Cho, I. K., Li, C., Zhang, X., Patel, S., Rusnak, R., Raper, J., Bachevalier, J., Moran, S. P., Chi, T., et al. (2022) · Aging Brain · doi:10.1016/j.nbas.2022.100044 · Cited by 10 · see citing works
Delport, A., Kins, S., & Hewer, R. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05364-z · Cited by 8 · see citing works
Developments in MRI radiomics research for vascular cognitive impairment
Chen, X., Luo, X., Chen, L., Liu, H., Yin, X., & Chen, Z. (2025) · Insights into Imaging · doi:10.1186/s13244-025-02026-1 · Cited by 7 · see citing works
Falgàs, N., Maure‐Blesa, L., Ances, B. M., Aguilar, L. F., Hartley, S. L., Hassenstab, J. J., Iulita, M. F., Janicki, M. P., Koenig, K. A., Lao, P. J., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70309 · Cited by 7 · see citing works
Self-citationSharma, A., & Singh, T. G. (2025) · Brain Research · doi:10.1016/j.brainres.2025.150047 · Cited by 6 · see citing works
Distinct cerebral amyloid angiopathy patterns in adult Down syndrome
Szalárdy, L., Lee, S., Kim, A., & Kovács, G. G. (2025) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2025.123601 · Cited by 6 · see citing works
Pivtoraiko, V. N., Racic, T., Abrahamson, E. E., Villemagne, V. L., Handen, B. L., Lott, I. T., Head, E., & Ikonomović, M. D. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.728739 · Cited by 6 · see citing works
The Treatment of Dually Diagnosed Individuals with Sleep Disturbances and Intellectual Disabilities
McPherson, P., Kaushal, M., & Kothapalli, V. (2020) · Autism and child psychopathology series · doi:10.1007/978-3-030-46835-4_36 · Cited by 5 · see citing works
What Can We Learn About Alzheimer’s Disease from People with Down Syndrome?
Maure‐Blesa, L., Rodríguez‐Baz, Í., Carmona‐Iragui, M., & Fortea, J. (2024) · Current topics in behavioral neurosciences · doi:10.1007/7854_2024_546 · Cited by 5 · see citing works
Costa, A. C. S. (2024) · Brain Sciences · doi:10.3390/brainsci14111084 · Cited by 4 · see citing works
Amyloid‐β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly
Okamoto, K., Amari, M., Fukuda, T., Suzuki, K., & Takatama, M. (2020) · Neuropathology · doi:10.1111/neup.12662 · Cited by 4 · see citing works
Kalfon, L., Paz, R., Raveh-Barak, H., Salama, A., Samra, N. N., Kaplun, A., Chasnyk, N., Kfir, N. C., Mousa, N. K., Biton, E. S., et al. (2022) · Current Alzheimer Research · doi:10.2174/1567205020666221020095257 · Cited by 4 · see citing works
Cannavo, C., Tosh, J., Fisher, E., & Wiseman, F. K. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.004 · Cited by 4 · see citing works
Mkhitaryan, E. A., Fateeva, V. V., & Kamchatnov, P. R. (2024) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202412402185 · Cited by 3 · see citing works
The role of cerebrovascular disease in aging and Alzheimer's disease among people with Down syndrome
Rizvi, B. M., Head, E., & Brickman, A. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818845-3.00012-8 · Cited by 2 · see citing works
Alzheimer's disease in Down syndrome: progress and promise
Ryan, N. S. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00276-5 · Cited by 1 · see citing works
Shimohama, S., Azami, S., Oyama, M., Takizawa, T., Kubota, M., Suzuki, H., Yamada, M., Nakahara, J., & Ito, D. (2026) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251412896 · Cited by 1 · see citing works
Aguilar, L. F., Zaikos, T. D., Rivera, I., Wright, S. T., Lou, J., Gawronski, B., Gonzalez, L., Berry, J. V., Rouanet, J. P., Edwards, N. C., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03028-z · Cited by 1 · see citing works
Biomarkers of Cognitive Decline and Dementia in Down Syndrome
Pais, M. V., Talib, L. L., & Forlenza, O. V. (2023) · Springer eBooks · doi:10.1007/978-3-031-43356-6_12 · Cited by 1 · see citing works
You, Q., Wang, W., Tao, T., Wang, T., Zhang, D., & Wang, L. (2022) · Journal of Biomaterials and Tissue Engineering · doi:10.1166/jbt.2022.2959
The Treatment of Dually Diagnosed Individuals with Sleep Disturbances and Intellectual Disabilities
Monceaux, B., Smith, K., & McPherson, P. (2024) · Autism and child psychopathology series · doi:10.1007/978-3-031-66902-6_16
Lloyd, G. M., Trejo‐Lopez, J. A., Xia, Y., McFarland, K. N., Lincoln, S., Ertekin-Taner, N., Giasson, B. I., Yachnis, A. T., & Prokop, S. (2020) · Figshare · doi:10.6084/m9.figshare.11978586
Lloyd, G. M., Trejo‐Lopez, J. A., Xia, Y., McFarland, K. N., Lincoln, S., Ertekin-Taner, N., Giasson, B. I., Yachnis, A. T., & Prokop, S. (2020) · Figshare · doi:10.6084/m9.figshare.11978577
Lloyd, G. M., Trejo‐Lopez, J. A., Xia, Y., McFarland, K. N., Lincoln, S., Ertekin-Taner, N., Giasson, B. I., Yachnis, A. T., & Prokop, S. (2020) · Figshare · doi:10.6084/m9.figshare.11978583
Mechanisms of Dural Involvement in Cerebral Amyloid Angiopathy
Zedde, M., Piazza, F., & Pascarella, R. (2025) · Cells · doi:10.3390/cells15010026
The Use of Localized Proteomics to Understand the Pathogenesis of Alzheimer's Disease
Pires, G. (2021) · theses.fr (ABES) · doi:10.70675/45826fd6zd2c8z4b3dz91e0za5080544cb17
McGlinchey, E., Pape, S., Zaman, S. H., Eustace‐Cook, J., Stockbauer, A., Baldimtsi, E. N., Langballe, E. M., Larsen, F., Sandkühler, K., Ivain, P., et al. (2026) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-026-09694-0
Self-citationAngiopathie amyloïde cérébrale héréditaire
Grangeon, L., Nicolas, G., & Wallon, D. (2026) · Encyclopédie médico-chirurgicale. Neurologie · doi:10.1016/s0246-0378(26)49255-6
Multiomics and proteomic insights into Alzheimer’s disease biology in Down syndrome
Martá-Ariza, M., & Wisniewski, T. R. (2026) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2026.2695187
- Authors
- Mann, D. M. A., Davidson, Y. S., Robinson, A. C., Allen, N., Hashimoto, T., Richardson, A., Jones, M., Snowden, J. S., Pendleton, N., Potier, M.-C., Laquerrière, A., Prasher, V., Iwatsubo, T., & Strydom, A.
- Affiliations
- University of Manchester (GB)
- The University of Tokyo (JP)
- Salford Royal Hospital (GB)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Birmingham Community Healthcare NHS Trust (GB)
- Corresponding author
- Mann, David M. A.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2018-05-16
- Volume
- 136
- Issue
- 4
- Pages
- 569-587
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC6132946
- OpenAlex
- W2803318546
- Cited by
- 73
- References
- 51
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 15 · 2019: 6 · 2018: 1
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- HAL (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (098330/Z/12/Z)
- Alzheimer's Society
- Medical Research Council (MR/L022656/1)
- Japan Society for the Promotion of Science (17H04193, 18K07364)
- 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 › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- Alzheimer's disease, cerebral amyloid angiopathy, Down syndrome, amyloid plaques, APOE ε4, vascular amyloid
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Apolipoproteins E, Blood Vessels, Down Syndrome, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, Mutation, Missense, Gene Duplication, Plaque, Amyloid
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