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Nat Commun. 2016 Jun 21;7:11934. doi: 10.1038/ncomms11934.

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis.

Collaborators (310)

Weiner MW, Aisen P, Petersen R, Jack CR, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Shaw LM, Khachaturian Z, Sorensen G, Kuller L, Raichle M, Paul S, Davies P, Fillit H, Hefti F, Holtzman D, Mesulam MM, Potter W, Snyder P, Schwartz A, Montine T, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Harvey D, Bernstein M, Fox N, Thompson P, Schuff N, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Landau S, Cairns NJ, Householder E, Taylor-Reinwald L, Lee V, Korecka M, Figurski M, Crawford K, Neu S, Foroud TM, Potkin S, Shen L, Faber K, Kim S, Nho K, Thal L, Buckholtz N, Albert M, Frank R, Hsiao J, Kaye J, Quinn J, Lind B, Carter R, Dolen S, Schneider LS, Pawluczyk S, Beccera M, Teodoro L, Spann BM, Brewer J, Vanderswag H, Fleisher A, Heidebrink JL, Lord JL, Mason SS, Albers CS, Knopman D, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Rountree S, Dang M, Stern Y, Honig LS, Bell KL, Ances B, Carroll M, Leon S, Mintun MA, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Grossman H, Mitsis E, de Toledo-Morrell L, Shah RC, Duara R, Varon D, Greig MT, Roberts P, Albert M, Onyike C, D'Agostino D, Kielb S, Galvin JE, Cerbone B, Michel CA, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy PM, Petrella JR, Wong TZ, Arnold SE, Karlawish JH, Wolk D, Smith CD, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Ismail MS, Brand C, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Swerdlow RH, Apostolova L, Tingus K, Woo E, Silverman DH, Lu PH, Bartzokis G, Graff-Radford NR, Parfitt F, Kendall T, Johnson H, Farlow MR, Hake A, Matthews BR, Herring S, Hunt C, van Dyck CH, Carson RE, MacAvoy MG, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung GY, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Bernick C, Munic D, Kerwin D, Mesulam MM, Lipowski K, Wu CK, Johnson N, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Frey M, Lane B, Rosen A, Tinklenberg J, Sabbagh MN, Belden CM, Jacobson SA, Sirrel SA, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Allard J, Lerner A, Ogrocki P, Hudson L, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Adeli A, Zimmerman EA, Celmins D, Brown AD, Pearlson GD, Blank K, Anderson K, Santulli RB, Kitzmiller TJ, Schwartz ES, Sink KM, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Spicer K, Bachman D, Finger E, Pasternak S, Rachinsky I, Drost D, Pomara N, Hernando R, Sarrael A, Schultz SK, Ponto LL, Shim H, Smith KE, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj BA, Neylan T, Grafman J, Davis M, Morrison R, Hayes J, Finley S, Friedl K, Fleischman D, Arfanakis K, James O, Massoglia D, Fruehling JJ, Harding S, Peskind ER, Petrie EC, Li G, Yesavage JA, Taylor JL, Furst AJ.

Author information

1
Department of Neurology &Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
2
Ludmer Centre for NeuroInformatics and Mental Health, Montreal, Quebec, Canada H3A 2B4.
3
Department of Radiology and Hotchkiss Brain institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

Abstract

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

PMID:
27327500
PMCID:
PMC4919512
DOI:
10.1038/ncomms11934
[Indexed for MEDLINE]
Free PMC Article

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