MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease.
The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD.
Helpern
Joseph A
JA
Nathan S Kline Institute, Orangeburg, New York 10962, USA. helpern@nki.rfmh.org
Lee
Sang-Pil
SP
Falangola
Maria F
MF
Dyakin
Victor V
VV
Bogart
Adam
A
Ardekani
Babak
B
Duff
Karen
K
Branch
Craig
C
Wisniewski
Thomas
T
de Leon
Mony J
MJ
Wolf
Oliver
O
O'Shea
Jacqueline
J
Nixon
Ralph A
RA
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology*; D003337:Corpus Callosum / Q000473:pathology; D004195:Disease Models, Animal; D006179:Gyrus Cinguli / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1