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Mol Neurobiol. 2018 Nov 9. doi: 10.1007/s12035-018-1405-1. [Epub ahead of print]

Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer's Dementia.

Collaborators (240)

Weiner MW, Aisen P, Petersen R, Jack RCR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Shaw LM, Kaye J, Quinn J, Silbert L, 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, Morris JC, Carroll M, Creech ML, Franklin E, Mintun MA, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Love MN, Grossman H, Mitsis E, Shah RC, de Shah Toledo-Morrell L, Duara R, Varon D, Greig MT, Roberts P, Albert M, Onyike C, D'Agostino D, Kielb S, Galvin JE, Cerbone B, Michel CA, Pogorelec DM, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy PM, Petrella JR, Borges-Neto S, Wong TZ, Coleman E, Smith CD, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Saleem Ismail M, Brand C, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Levey AI, Lah JJ, Cellar JS, Burns JM, Swerdlow RH, Brooks WM, Apostolova L, Tingus K, Woo E, Silverman DHS, Lu PH, Bartzokis G, Graff-Radford NR, Parfitt F, Kendall T, Johnson H, Farlow MR, Hake AM, Matthews BR, Brosch JR, Herring S, Hunt C, van Dyck CH, Carson RE, MacAvoy MG, Varma P, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung GR, Feldman H, Mudge B, Assaly M, Finger E, Pasternack S, Rachisky I, Trost D, Kertesz A, Bernick C, Munic D, Mesulam MM, Lipowski K, Weintraub S, Bonakdarpour B, Kerwin D, Wu CK, Johnson N, Sadowsky C, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Yesavage J, Taylor JL, Lane B, Rosen A, Tinklenberg J, Sabbagh MN, Belden CM, Jacobson SA, Sirrel SA, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Obisesan TO, Wolday S, Allard J, Lerner A, Ogrocki P, Tatsuoka C, Fatica P, Fletcher E, Maillard P, Olichney J, DeCarli C, Carmichael O, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Burke A, Trncic N, Fleisher A, 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, Flashman LA, Seltzer M, Hynes ML, Santulli RB, Sink KM, Gordineer L, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Perry D, Mintzer J, Spicer K, Bachman D, Pomara N, Hernando R, Sarrael A, Relkin N, Chaing G, Lin M, Ravdin L, Smith A, Raj BA, Fargher K.

Author information

1
Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health Research Institute, 6825, boul. LaSalle Blvd., Montréal, QC, H4H1R3, Canada.
2
Alzheimer's Disease Research Unit, MCSA, Douglas Mental Health Research Institute, Montréal, Canada.
3
Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
4
Department of Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
5
Graduate Program in Biological Science: Biochemistry, UFRGS, Porto Alegre, Brazil.
6
Graduate Program in Biological Sciences: Pharmacology and Therapeutics, UFRGS, Porto Alegre, Brazil.
7
Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health Research Institute, 6825, boul. LaSalle Blvd., Montréal, QC, H4H1R3, Canada. pedro.rosa@mcgill.ca.
8
Alzheimer's Disease Research Unit, MCSA, Douglas Mental Health Research Institute, Montréal, Canada. pedro.rosa@mcgill.ca.

Abstract

We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer's disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.

KEYWORDS:

Alzheimer’s disease; Amyloid-β (Aβ); Diffusion tensor imaging (DTI); Interaction; Positron emission tomography (PET); White matter (WM)

PMID:
30414086
DOI:
10.1007/s12035-018-1405-1

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