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Nat Neurosci. 2013 Jul;16(7):848-50. doi: 10.1038/nn.3435. Epub 2013 May 23.

CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology.

Collaborators (327)

Weiner MW, Aisen P, Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Shaw LM, Khachaturian Z, Sorensen G, Carrillo M, Kuller L, Raichle M, Paul S, Davies P, Fillit H, Hefti F, Holtzman D, Mesulam M, Potter W, Snyder P, Schwartz A, Green RC, Montine T, Petersen R, Aisen P, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Jiminez G, Beckett L, Harvey D, Donohue M, Jack CR Jr, Bernstein M, Fox N, Thompson P, Schuff N, DeCArli C, Borowski B, Gunter J, Senjem M, Vemuri P, Jones D, Kantarci K, Ward C, Jagust W, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Landau S, Morris JC, Cairns NJ, Householder E, Taylor-Reinwald L, Shaw LM, Trojanowki JQ, Lee V, Korecka M, Figurski M, Toga AW, Crawford K, Neu S, Saykin AJ, Foroud TM, Potkin S, Shen L, Faber K, Kim S, Nho K, Weiner MW, Thal L, Khachaturian Z, Thal L, Buckholtz N, Weiner MW, Snyder PJ, Potter W, Paul S, Albert M, Frank R, Khachaturian Z, 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, Petersen R, 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, Leon S, Householder E, Mintun MA, Schneider S, Oliver A, Marson D, Griffith R, Clark D, Geldmacher D, Brockington J, Roberson E, Grossman H, Mitsis E, deToledo-Morrell L, Shah RC, Duara R, Varon D, Greig MT, Roberts P, Albert M, Onyike C, D'Agostino D 2nd, Kielb S, Galvin JE, Pogorelec DM, Cerbone B, Michel CA, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy P, 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 M, 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 AM, 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, Trost D, 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, 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, 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, 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, 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, Rogers J, Kertesz A, 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.

Abstract

In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 × 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

PMID:
23708142
[PubMed - indexed for MEDLINE]
PMCID:
PMC3703870
Free PMC Article

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