Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis

被引:46
作者
Mueggler, T
Meyer-Luehmann, M
Rausch, M
Staufenbiel, M
Jucker, M
Rudin, M [3 ]
机构
[1] Univ Basel, Inst Pathol, Dept Neuropathol, CH-4003 Basel, Switzerland
[2] Univ Tubingen, Dept Cellular Neurol, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany
[3] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland
关键词
Alzheimer's disease; apparent diffusion coefficient; beta-amyloid; magnetic resonance imaging; transgenic mice;
D O I
10.1111/j.1460-9568.2004.03534.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A prominent hallmark of Alzheimer's disease pathology is cerebral amyloidosis. However, it is not clear how extracellular amyloid-beta peptide (Abeta) deposition and amyloid formation compromise brain function and lead to dementia. It has been argued that extracellular amyloid deposition is neurotoxic and/or that soluble Abeta oligomers impair synaptic function. Amyloid deposits, by contrast, may affect diffusion properties of the brain interstitium with implications for the transport of endogenous signalling molecules during synaptic and/or extrasynaptic transmission. We have used diffusion-weighted magnetic resonance imaging to study diffusion properties in brains of young (6-month-old) and aged (25-month-old) APP23 transgenic mice and control littermates. Our results demonstrate that fibrillar amyloid deposits and associated gliosis in brains of aged APP23 transgenic mice are accompanied by a reduction in the apparent diffusion coefficient. This decrease was most pronounced in neocortical areas with a high percentage of congophilic amyloid and was not significant in the caudate putamen, an area with only modest and diffuse amyloid deposition. These findings suggest that extracellular deposition of fibrillar amyloid and/or associated glial proliferation and hypertrophy cause restrictions to interstitial fluid diffusion. Reduced diffusivity within the interstitial space may alter volume transmission and therefore contribute to the cognitive impairment in Alzheimer's disease.
引用
收藏
页码:811 / 817
页数:7
相关论文
共 39 条
[1]   Inflammation and Alzheimer's disease [J].
Akiyama, H ;
Barger, S ;
Barnum, S ;
Bradt, B ;
Bauer, J ;
Cole, GM ;
Cooper, NR ;
Eikelenboom, P ;
Emmerling, M ;
Fiebich, BL ;
Finch, CE ;
Frautschy, S ;
Griffin, WST ;
Hampel, H ;
Hull, M ;
Landreth, G ;
Lue, LF ;
Mrak, R ;
Mackenzie, IR ;
McGeer, PL ;
O'Banion, MK ;
Pachter, J ;
Pasinetti, G ;
Plata-Salaman, C ;
Rogers, J ;
Rydel, R ;
Shen, Y ;
Streit, W ;
Strohmeyer, R ;
Tooyoma, I ;
Van Muiswinkel, FL ;
Veerhuis, R ;
Walker, D ;
Webster, S ;
Wegrzyniak, B ;
Wenk, G ;
Wyss-Coray, T .
NEUROBIOLOGY OF AGING, 2000, 21 (03) :383-421
[2]   MECHANISM OF DETECTION OF ACUTE CEREBRAL-ISCHEMIA IN RATS BY DIFFUSION-WEIGHTED MAGNETIC-RESONANCE MICROSCOPY [J].
BENVENISTE, H ;
HEDLUND, LW ;
JOHNSON, GA .
STROKE, 1992, 23 (05) :746-754
[3]   Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice [J].
Bondolfi, L ;
Calhoun, M ;
Ermini, F ;
Kuhn, HG ;
Wiederhold, KH ;
Walker, L ;
Staufenbiel, M ;
Jucker, M .
JOURNAL OF NEUROSCIENCE, 2002, 22 (02) :515-522
[4]  
Bornemann KD, 2001, AM J PATHOL, V158, P63, DOI 10.1016/S0002-9440(10)63945-4
[5]  
Bozzao A, 2001, AM J NEURORADIOL, V22, P1030
[6]   Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid [J].
Calhoun, ME ;
Burgermeister, P ;
Phinney, AL ;
Stalder, M ;
Tolnay, M ;
Wiederhold, KH ;
Abramowski, D ;
Sturchler-Pierrat, C ;
Sommer, B ;
Staufenbiel, M ;
Jucker, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14088-14093
[7]   Neuron loss in APP transgenic mice [J].
Calhoun, ME ;
Wiederhold, KH ;
Abramowski, D ;
Phinney, AL ;
Probst, A ;
Sturchler-Pierrat, C ;
Staufenbiel, M ;
Sommer, B ;
Jucker, M .
NATURE, 1998, 395 (6704) :755-756
[8]  
Franklin K. B. J., 2013, PAXINOS FRANKLINS MO
[9]  
Frautschy SA, 1998, AM J PATHOL, V152, P307
[10]   Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease [J].
Hanyu, H ;
Sakurai, H ;
Iwamoto, T ;
Takasaki, M ;
Shindo, H ;
Abe, K .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1998, 156 (02) :195-200