Reduced brain tissue perfusion in TGF-β1 transgenic mice showing Alzheimer's disease-like cerebrovascular abnormalities

被引:42
作者
Gaertner, RF
Wyss-Coray, T
Von Euw, D
Lesné, S
Vivien, D
Lacombe, P
机构
[1] Univ Paris 07, CNRS, UPR 646, Lab Rech Cerebrovasc, Paris, France
[2] Stanford Univ, Med Ctr, Dept Neurol, Stanford, CA 94305 USA
[3] Univ Caen, CNRS, UMR 6551, F-14074 Caen, France
基金
美国国家卫生研究院;
关键词
cerebral blood flow; cerebral glucose utilization; cerebral amyloid angiopathy; cytokine; TGF-beta 1 transgenic mice; thioflavin-S;
D O I
10.1016/j.nbd.2004.11.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have studied the functional repercussions of cerebrovascular abnormalities in transgenic mice overexpressing TGF-beta 1. These mice develop Alzheimer's disease-like vascular and meningeal alterations without parenchymal degeneration. Autoradiographic cerebral blood flow measurements in 9-month-old TGF-beta 1 mice compared to non-transgenic littermates provided evidence of reduced tissue perfusion, most prominent in limbic regions. A highly significant inverse correlation was found between the density of thioflavin-S-positive blood vessels and blood flow in the hippocampus and the cortex. An inverse correlation was likewise found between meningeal staining and blood flow in thalamic nuclei and regions of high blood flow. Thus, the vascular abnormalities were associated locally with reduced perfusion rate and more widely with limitation in the blood flow. These chronic changes may he related to fibrillar and soluble A beta peptides, the amount of which was almost doubled in the brains of TGF-beta 1 mice. Comparison with previous results of cerebral glucose utilization in TGF-beta 1 mice shows that reduced utilization preferentially occurred in regions with a high metabolic rate and a relatively low blood flow, suggesting that the metabolic needs are not met by blood supply in these regions. (c) 2004 Published by Elsevier Inc.
引用
收藏
页码:38 / 46
页数:9
相关论文
共 49 条
[1]   β-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase [J].
Abramov, AY ;
Canevari, L ;
Duchen, MR .
JOURNAL OF NEUROSCIENCE, 2004, 24 (02) :565-575
[2]   Progression of cerebral amyloid angiopathy:: Accumulation of amyloid-β40 in affected vessels [J].
Alonzo, NC ;
Hyman, BT ;
Rebeck, GW ;
Greenberg, SM .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1998, 57 (04) :353-359
[3]   Characterization of new polyclonal antibodies specific for 40 and 42 amino acid long amyloid beta peptides: Their use to examine the cell biology of presenilins and the immunohistochemistry of sporadic Alzheimer's disease and cerebral amyloid angiopathy cases [J].
Barelli, HL ;
Lebeau, A ;
Vizzavona, J ;
Delaere, P ;
Chevallier, N ;
Drouot, C ;
Marambaud, P ;
Ancolio, K ;
Buxbaum, JD ;
Khorkova, O ;
Heroux, J ;
Sahasrabudhe, S ;
Martinez, J ;
Warter, JM ;
Mohr, M ;
Checler, F .
MOLECULAR MEDICINE, 1997, 3 (10) :695-707
[4]   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
[5]   β-amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons [J].
Casley, CS ;
Land, JM ;
Sharpe, MA ;
Clark, JB ;
Duchen, MR ;
Canevari, L .
NEUROBIOLOGY OF DISEASE, 2002, 10 (03) :258-267
[6]   Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy [J].
Christie, R ;
Yamada, M ;
Moskowitz, M ;
Hyman, B .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (03) :1065-1071
[7]   RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain [J].
Deane, R ;
Yan, SD ;
Submamaryan, RK ;
LaRue, B ;
Jovanovic, S ;
Hogg, E ;
Welch, D ;
Manness, L ;
Lin, C ;
Yu, J ;
Zhu, H ;
Ghiso, J ;
Frangione, B ;
Stern, A ;
Schmidt, AM ;
Armstrong, DL ;
Arnold, B ;
Liliensiek, B ;
Nawroth, P ;
Hofman, F ;
Kindy, M ;
Stern, D ;
Zlokovic, B .
NATURE MEDICINE, 2003, 9 (07) :907-913
[8]   Plaque-associated disruption of CSF and plasma amyloid-β (Aβ) equilibrium in a mouse model of Alzheimer's disease [J].
DeMattos, RB ;
Bales, KR ;
Parsadanian, M ;
O'Dell, MA ;
Foss, EM ;
Paul, SM ;
Holtzman, DM .
JOURNAL OF NEUROCHEMISTRY, 2002, 81 (02) :229-236
[9]   Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease [J].
Esiri, MM ;
Nagy, Z ;
Smith, MZ ;
Barnetson, L ;
Smith, AD .
LANCET, 1999, 354 (9182) :919-920
[10]   Cerebral microvascular pathology in aging and Alzheimer's disease [J].
Farkas, E ;
Luiten, PGM .
PROGRESS IN NEUROBIOLOGY, 2001, 64 (06) :575-611