AT(N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome.
ATN
Alzheimer's
Down syndrome
adults
amyloid
biomarker
cognitive
dementia
hippocampal
imaging
magnetic resonance imaging
memory
positron emission tomography
tau
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
28 Aug 2023
28 Aug 2023
Historique:
revised:
01
08
2023
received:
30
05
2023
accepted:
02
08
2023
medline:
29
8
2023
pubmed:
29
8
2023
entrez:
29
8
2023
Statut:
aheadofprint
Résumé
Down syndrome (DS) is a genetic cause of early-onset Alzheimer's disease (AD). The National Institute on Aging-Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS. Data are from the Alzheimer's Biomarker Consortium-Down Syndrome. Positron emission tomography (PET) amyloid beta (Aβ; 15 mCi of [ Analyses included 162 adults with DS (aged M = 38.84 years, standard deviation = 8.41). Overall, 69.8% of participants were classified as A-/T-/(N)-, 11.1% were A+/T-/(N)-, 5.6% were A+/T+/(N)-, and 9.3% were A+/T+/(N)+. Participants deemed cognitively stable were most likely to be A-T-(N)- and A+T-(N)-. Tau PET (T+) most closely aligning with memory impairment and AD clinical status. Findings add to understanding of AT(N) biomarker profiles in DS. Overall, 69.8% of adults with Down syndrome (DS) aged 25 to 61 years were classified as amyloid (A)-/tau (T)-/neurodegeneration (N)-, 11.1% were A+/T-/(N)-, 5.6% were A+/T+/(N)-, and 9.3% were A+/T+/(N)+. The AT(N) profiles were associated with clinical Alzheimer's disease (AD) status and with memory performance, with the presence of T+ aligned with AD clinical symptomology. Findings inform models for predicting the transition to the prodromal stage of AD in DS.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : U01 AG051406
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG051412
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG068054
Pays : United States
Informations de copyright
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M. Alzheimer's disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021;20(11):930-942. doi:10.1016/S1474-4422(21)00245-3
Wiseman FK, Al-Janabi T, Hardy J, et al. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neuro. 2015;16(9):564-574. doi:10.1038/nrn3983
Jack CR Jr, DM H. Biomarker modeling of Alzheimer's disease. Neuron. 2013;80(6):1347-1358. doi:10.1016/j.neuron.2013.12.003
Hardy JA, Higgings GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992;256:184-185. doi:10.1126/science.1566067
Iulita MF, Garzón Chavez D, Klitgaard Christensen M, et al. Association of Alzheimer Disease with life expectancy in people with Down syndrome. JAMA Netw Open. 2022;5(5):e2212910-e2212910. doi:10.1001/jamanetworkopen.2022.12910
McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Dis Res. 2017;61(9):843-852. doi:10.1111/jir.12390
Hithersay R, Startin CM, Hamburg S, et al. Association of dementia with mortality among adults with Down syndrome older than 35 years. JAMA Neurol. 2019;76(2):152-160.
Fortea J, Vilaplana E, Carmona-Iragui M, et al. Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study. Lancet North Am Ed. 2020;395(10242):1988-1997.
Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019;15(3):135-147. doi:10.1038/s41582-018-0132-6
Rafii MS, Ances BM, Schupf N, et al. The AT (N) framework for Alzheimer's disease in adults with Down syndrome. Alz & Dem: diagnosis. Assess Dis Monitor. 2020;12(1):e12062.
Lao PJ, Handen BL, Betthauser TJ, et al. Imaging neurodegeneration in Down syndrome: brain templates for amyloid burden and tissue segmentation. Brain Imaging Behav. 2019;13(2):345-353. doi:10.1007/s11682-018-9888-y
Lao PJ, Handen BL, Betthauser TJ, et al. Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population. Alzheimer's Dement (Amst). 2017;9:1-9.
Zammit MD, Tudorascu DL, Laymon CM, et al. Neurofibrillary tau depositions emerge with subthreshold cerebral beta-amyloidosis in down syndrome. Neuroimage Clin. 2021;31:102740. doi:10.1016/j.nicl.2021.102740
Rafii MS. Tau PET imaging for staging of Alzheimer's disease in Down syndrome. Develop Neurobiol. 2019;79(7):711-715.
Tudorascu DL, Laymon CM, Zammit M, et al. Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline. Alzheimer's Dement. Transl Res Clin Interv. 2020;6(1):e12096.
Teipel SJ, Hampel H. Neuroanatomy of Down syndrome in vivo: a model of preclinical Alzheimer's disease. Behav Genetics. 2006;36:405-415.
Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Annals of Neurology: Official J Amer Neurol Assoc Child Neurol Soc. 1985;17(3):278-282.
Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron. 2013;80(6):1347-1358.
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimer's Dement. 2018;14(4):535-562.
Annus T, Wilson LR, Hong YT, et al. The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimer's Dement. 2016;12(5):538-545.
Hartley SL, Handen BL, Devenny D, et al. Cognitive indicators of transition to preclinical and prodromal stages of Alzheimer's disease in Down syndrome. Alzheimers Dement (Amst). 2020;12(1):e12096. doi:10.1002/dad2.12096
Hartley SL, Handen BL, Tudorascu D, et al. Role of tau deposition in early cognitive decline in Down syndrome. Alzheimers Dement (Amst). 2022;14(1):e12256. doi:10.1002/dad2.12256
Grigorova M, Mak E, Brown SS, et al. Amyloid-β and tau deposition influences cognitive and functional decline in Down syndrome. Neurobiol of Aging. 2022;119:36-45.
Jack CR, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010;9(1):119-128.
Jack Jr CR, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-562.
Jack CR, Bennett DA, Blennow K, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurol. 2016;87(5):539-547.
Roid G, Stanford Binet Intelligence Scales. Itasca, IL :Riverside Pub. 2003
Handen BL, Lott IT, Christian BT, et al. The Alzheimer's Biomarker Consortium-Down Syndrome: rationale and methodology. Alzheimers Dement (Amst). 2020;12(1):e12065. doi:10.1002/dad2.12065
Zimmerli E, Devenny DA, Paper presented at the Gatlinburg conference on research and theory in mental retardation and developmental disabilities. Cued recall as a screen for dementia in the MR population. 1995. Gatlinburg, TN
Devenny DA, Zimmerli EJ, Kittler P, Krinsky-McHale SJ. Cued recall in early-stage dementia in adults with Down's syndrome. J Intellect Disabil Res. 2002;46(Pt 6):472-483. doi:10.1046/j.1365-2788.2002.00417.x
Bigler ED, Skiles M, Wade BSC, et al. FreeSurfer 5.3 versus 6.0: are volumes comparable? A Chronic Effects of Neurotrauma Consortium study. Brain Imaging Behav. 2020;14(5):1318-1327. doi:10.1007/s11682-018-9994-x
Desikan RS, Ségonne F, Fischl B, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31(3):968-980. doi:10.1016/j.neuroimage.2006.01.021
Mosconi L, De Santi S, Li J, et al. Hippocampal hypometabolism predicts cognitive decline from normal aging. Neurobiol Aging. 2008;29(5):676-692. doi:10.1016/j.neurobiolaging.2006.12.008
Klunk WE, Koeppe RA, Price JC, et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11(1):1-15. doi:10.1016/j.jalz.2014.07.003. e1-4. Epub 2014 Oct 28. PMID: 25443857; PMCID: PMC4300247.
Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011;54(3):2033-2044. doi:10.1016/j.neuroimage.2010.09.025. Epub 2010 Sep 17. PMID: 20851191; PMCID: PMC3065962.
Avants BB, Epstein CL, Grossman M, Gee JC. (2007). Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal. 2008;12(1):26-41. doi:10.1016/j.media.2007.06.004
Jack CR, Wiste HJ, Weigand SD, et al. Defining imaging biomarker cut points for brain aging and Alzheimer's disease. Alzheimers Dement. 2017;13(3):205-216. doi:10.1016/j.jalz.2016.08.005
Zammit MD, Laymon CM, Betthauser TJ, et al. Amyloid accumulation in Down syndrome measured with amyloid load. Alzheimers Dement (Amst). 2020;12(1):e12020. doi:10.1002/dad2.12020
Delmotte K, Schaeverbeke J, Poesen K, Vandenberghe R. Prognostic value of amyloid/tau/neurodegeneration (ATN) classification based on diagnostic cerebrospinal fluid samples for Alzheimer's disease. Alzheimer's. Research & Therapy. 2021;13:1-3.
Ezzati A, Abdulkadir A, Jack Jr CR, et al. Alzheimer's Disease Neuroimaging Initiative, Lipton RB. Predictive value of ATN biomarker profiles in estimating disease progression in Alzheimer's disease dementia. Alzheimer's Demen. 2021;17(11):1855-1867.
Tan MS, Ji X, Li JQ, et al. Longitudinal trajectories of Alzheimer's ATN biomarkers in elderly persons without dementia. Alzheimer's research & therapy. 2020;12:1-7.
Oberstein TJ, Schmidt MA, Florvaag A, et al. Amyloid-β levels and cognitive trajectories in non-demented pTau181-positive subjects without amyloidopathy. Brain. 2022;145(11):4032-4041.
Hanseeuw BJ, Betensky RA, Jacobs HIL, et al. Association of amyloid and tau with cognition in preclinical Alzheimer disease: a longitudinal study. JAMA Neurol. 2019;76(8):915-924. doi:10.1001/jamaneurol.2019.1424
Ossenkoppele R, Smith R, Mattsson-Carlgren N, et al. Accuracy of tau positron emission tomography as a prognostic marker in preclinical and prodromal Alzheimer disease: a head-to-head comparison against amyloid positron emission tomography and magnetic resonance imaging. JAMA Neurol. 2021;78(8):961-971. doi:10.1001/jamaneurol.2021.1858
Gordon BA, Blazey TM, Christensen J, Benzinger TLS. Tau PET in autosomal dominant Alzheimer's disease: relationship with cognition, dementia and other biomarkers. Brain. 2019;142(4):1063-1076. doi:10.1093/brain/awz019
Dekker AD, Sacco S, Carfi A, et al. Deyn PP. The behavioral and psychological symptoms of dementia in Down syndrome (BPSD-DS) Scale: comprehensive Assessment of Psychopathology in Down Syndrome. J Alzheimers Dis. 2018;63(2):797-819. doi:10.3233/JAD-170920
Ball SL, Holland AJ, Hon J, Huppert FA, Treppner P, Watson PC. Personality and behaviour changes mark the early stages of Alzheimer's disease in adults with Down's syndrome: findings from a prospective population-based study. Int J Geriatr Psychiatry. 2006;21(7):661-673. doi:10.1002/gps.1545
Fonseca LM, Mattar GP, Haddad GG, et al. Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome. Neurobiol Aging. 2019;78:186-194. doi:10.1016/j.neurobiolaging.2019.02.028
Fonseca LM, Padilla C, Jones E, et al. Amnestic and non-amnestic symptoms of dementia: an international study of Alzheimer's disease in people with Down's syndrome. Int J Geriatr Psychiatry. 2020;35(6):650-661. doi:10.1002/gps.5283