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Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study

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dc.contributor.author Boerwinkle, Anna H.
dc.contributor.author Gordon, Brian A.
dc.contributor.author Wisch, Julie K.
dc.contributor.author Flores, Shaney
dc.contributor.author Henson, Rachel L.
dc.contributor.author Butt, Omar H.
dc.contributor.author McKay, Nicole S.
dc.contributor.author Chen, Charles D.
dc.contributor.author Benzinger, Tammie L.S.
dc.contributor.author Fagan, Anne M.
dc.contributor.author Handen, Benjamin L.
dc.contributor.author Christian, Bradley T.
dc.contributor.author Head, Elizabeth
dc.contributor.author Mapstone, Mark
dc.contributor.author Rafii, Michael S.
dc.contributor.author Alzheimer's Biomarker Consortium-Down Syndrome
dc.contributor.author Dominantly Inherited Alzheimer Network
dc.contributor.author Allegri, Ricardo Francisco
dc.contributor.author Chrem Méndez, Patricio Alexis
dc.contributor.author Egido, Noelia
dc.date.accessioned 2023-03-02T14:46:30Z
dc.date.available 2023-03-02T14:46:30Z
dc.date.issued 2022-12-12
dc.identifier.citation Boerwinkle, A.H., Gordon, B.A., Wisch, J.K., Flores, S., Henson, R.L., Butt, O.H., McKay, N.S., Chen, C.D., Benzinger, T.L.S., Fagan, A.M., Handen, B.L., Christian, B.T., Head, E., Mapstone, M., Rafii, M.S., O’Bryant, S., Lai, F., Rosas, H.D., Lee, J.H., Silverman, W., Brickman, A.M., Chhatwal, J.P., Cruchaga, C., Perrin, R.J., Xiong, C., Hassenstab, J., McDade, E., Bateman, R.J., Ances, B.M., Aizenstein, H.J., Andrews, H.F., Bell, K., Birn, R.M., Bulova, P., Cheema, A., Chen, K., Clare, I., Clark, L., Cohen, A.D., Constantino, J.N., Doran, E.W., Feingold, E., Foroud, T.M., Hartley, S.L., Hom, C., Honig, L., Ikonomovic, M.D., Johnson, S.C., Jordan, C., Kamboh, M.I., Keator, D., Klunk MD, W.E., Kofler, J.K., Kreisl, W.C., Krinsky- McHale, S.J., Lao, P., Laymon, C., Lott, I.T., Lupson, V., Mathis, C.A., Minhas, D.S., Nadkarni, N., Pang, D., Petersen, M., Price, J.C., Pulsifer, M., Reiman, E., Rizvi, B., Sabbagh, M.N., Schupf, N., Tudorascu, D.L., Tumuluru, R., Tycko, B., Varadarajan, B., White, D.A., Yassa, M.A., Zaman, S., Zhang, F., Adams, S., Allegri, R., Araki, A., Barthelemy, N., Bechara, J., Berman, S., Bodge, C., Brandon, S., Brooks, W., Brosch, J., Buck, J., Buckles, V., Carter, K., Cash, L., Mendez, P.C., Chua, J., Chui, H., Courtney, L., Day, G., DeLaCruz, C., Denner, D., Diffenbacher, A., Dincer, A., Donahue, T., Douglas, J., Duong, D., Egido, N., Esposito, B., Farlow, M., Feldman, B., Fitzpatrick, C., Fox, N., Franklin, E., Joseph-Mathurin, N., Fujii, H., Gardener, S., Ghetti, B., Goate, A., Goldberg, S., Goldman, J., Gonzalez, A., Gräber-Sultan, S., Graff-Radford, N., Graham, M., Gray, J., Gremminger, E., Grilo, M., Groves, A., Haass, C., Häslerc, L., Hellm, C., Herries, E., Hoechst-Swisher, L., Hofmann, A., Holtzman, D., Hornbeck, R., Igor, Y., Ihara, R., Ikeuchi, T., Ikonomovic, S., Ishii, K., Jack, C., Jerome, G., Johnson, E., Jucker, M., Karch, C., Käser, S., Kasuga, K., Keefe, S., Klunk, W., Koeppe, R., Koudelis, D., Kuder-Buletta, E., Laske, C., Levey, A., Levin, J., Li, Y., Lopez, O., Marsh, J., Martins, R., Mason, N.S., Masters, C., Mawuenyega, K., McCullough, A., Mejia, A., Morenas-Rodriguez, E., Morris, J.C., Mountz, J., Mummery, C., Nadkarni, N., Nagamatsu, A., Neimeyer, K., Niimi, Y., Noble, J., Norton, J., Nuscher, B., Obermüller, U., O’Connor, A., Patira, R., Ping, L., Preische, O., Renton, A., Ringman, J., Salloway, S., Schofield, P., Senda, M., Seyfried, N.T., Shady, K., Shimada, H., Sigurdson, W., Smith, J., Smith, L., Snitz, B., Sohrabi, H., Stephens, S., Taddei, K., Thompson, S., Vöglein, J., Wang, P., Wang, Q., Weamer, E., Xu, J., Xu, X., 2023. Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer’s disease: a cross-sectional study. The Lancet Neurology 22, 55–65. https://doi.org/10.1016/S1474-4422(22)00408-2 es_ES
dc.identifier.uri https://doi.org/10.1016/S1474-4422(22)00408-2
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/794
dc.description.abstract Background: Important insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people. Methods: In this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated. Findings: 192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p<0·0001) and in people with Down syndrome (n=32; r=-0·801; p<0·0001). There was no difference in global PET amyloid burden between asymptomatic people with Down syndrome (mean 18·80 centiloids [SD 28·33]) versus asymptomatic mutation carriers (24·61 centiloids [30·27]; p=0·11) and between symptomatic people with Down syndrome (77·25 centiloids [41·76]) versus symptomatic mutation carriers (69·15 centiloids [51·10]; p=0·34). APOE ɛ4 status and sex had no effect on global amyloid PET deposition. Amyloid deposition was elevated significantly earlier in mutation carriers than in participants with Down syndrome (estimated years to symptom onset -23·0 vs -17·5; p=0·0002). PSEN1 mutations primarily drove this difference. Early amyloid accumulation occurred in striatal and cortical regions for both mutation carriers (n=265) and people with Down syndrome (n=128). Although mutation carriers had widespread amyloid accumulation in all cortical regions, the medial occipital regions were spared in people with Down syndrome. Interpretation: Despite minor differences, amyloid PET changes were similar between people with autosomal dominant Alzheimer's disease versus Down syndrome and strongly supported early amyloid dysregulation in individuals with Down syndrome. Individuals with Down syndrome aged at least 35 years might benefit from early intervention and warrant future inclusion in clinical trials, particularly given the relatively high incidence of Down syndrome. es_ES
dc.language.iso eng es_ES
dc.publisher Elsevier es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.subject Alzheimer Disease es_ES
dc.subject Enfermedad de Alzheimer es_ES
dc.subject Amyloid beta-Peptides es_ES
dc.subject Péptidos beta-Amiloides es_ES
dc.subject Cerebral Cortex es_ES
dc.subject Decorticación Cerebral es_ES
dc.subject Down Syndrome es_ES
dc.subject Síndrome de Down es_ES
dc.subject Down Syndrome
dc.subject Síndrome de Down
dc.title Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Boerwinkle, Anna H. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Gordon, Brian A. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Wisch, Julie K. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Flores, Shaney. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Henson, Rachel L. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Butt, Omar H. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: McKay, Nicole S. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Chen, Charles D. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Benzinger, Tammie L. S. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Fagan, Anne M. Washington University in St Louis; Estados Unidos.
dc.description.fil Fil: Handen, Benjamin L. University of Pittsburgh; Estados Unidos.
dc.description.fil Fil: Christian, Bradley T. University of Wisconsin-Madison; Estados Unidos.
dc.description.fil Fil: Head, Elizabeth. University of California Irvine School of Medicine; Estados Unidos.
dc.description.fil Fil: Mapstone, Mark. University of California Irvine School of Medicine; Estados Unidos.
dc.description.fil Fil: Rafii, Michael S. Keck School of Medicine of USC; Estados Unidos.
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.
dc.description.fil Fil: Chrem Méndez, Patricio Alexis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.
dc.description.fil Fil: Egido Noelia. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.
dc.relation.ispartofVOLUME 22
dc.relation.ispartofVOLUME 18
dc.relation.ispartofNUMBER 1
dc.relation.ispartofNUMBER Suppl. 6
dc.relation.ispartofPAGINATION 55-65
dc.relation.ispartofPAGINATION e064684
dc.relation.ispartofCOUNTRY Reino Unido
dc.relation.ispartofCITY Londres
dc.relation.ispartofTITLE Lancet Neurology
dc.relation.ispartofISSN 1474-4465
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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