Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging.
The presence of amyloid-beta (Abeta) plaques in the brain is a hallmark pathological feature of Alzheimer's disease (AD). Transgenic mice overexpressing mutant amyloid precursor protein (APP), or both mutant APP and presenilin-1 (APP/PS1), develop Abeta plaques similar to those in AD patients, and have been proposed as animal models in which to test experimental therapeutic approaches for the clearance of Abeta. However, at present there is no in vivo whole-brain imaging method to detect Abeta plaques in mice or men. A novel method is presented to detect Abeta plaques in the brains of transgenic mice by magnetic resonance microimaging (muMRI). This method uses Abeta1-40 peptide, known for its high binding affinity to Abeta, magnetically labeled with either gadolinium (Gd) or monocrystalline iron oxide nanoparticles (MION). Intraarterial injection of magnetically labeled Abeta1-40, with mannitol to transiently open the blood-brain barrier (BBB), enabled the detection of many Abeta plaques. Furthermore, the numerical density of Abeta plaques detected by muMRI and by immunohistochemistry showed excellent correlation. This approach provides an in vivo method to detect Abeta in AD transgenic mice, and suggests that diagnostic MRI methods to detect Abeta in AD patients may ultimately be feasible.
Wadghiri
Youssef Zaim
YZ
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
Sigurdsson
Einar M
EM
Sadowski
Marcin
M
Elliott
James I
JI
Li
Yongsheng
Y
Scholtzova
Henrieta
H
Tang
Cheuk Ying
CY
Aguinaldo
Gilbert
G
Pappolla
Miguel
M
Duff
Karen
K
Wisniewski
Thomas
T
Turnbull
Daniel H
DH
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000493:pharmacokinetics; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D019786:Gadolinium DTPA; D007150:Immunohistochemistry; D007501:Iron; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D010087:Oxides; D010446:Peptide Fragments / Q000493:pharmacokinetics; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003287:Contrast Media; D008565:Membrane Proteins; D010087:Oxides; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); D007501:Iron; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide