Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ42 fibrils

被引：1210

作者：

Götz, J

Chen, F

van Dorpe, J

Nitsch, RM

机构：

[1] Univ Zurich, Div Psychiat Res, CH-8008 Zurich, Switzerland

[2] Katholieke Univ Leuven, Ctr Human Genet, Expt Genet Grp, Louvain, Belgium

来源：

SCIENCE | 2001年 / 293卷 / 5534期

关键词：

D O I：

10.1126/science.1062097

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

beta -Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta -amyloid A beta (42) fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after A beta (42) injections. Our data support the hypothesis that A beta (42) fibrils can accelerate NFT formation in vivo.

引用

收藏

页码：1491 / 1495

页数：5

相关论文

共 33 条

[1] The Topographical and Neuroanatomical Distribution of Neurofibrillary Tangles and Neuritic Plaques in the Cerebral Cortex of Patients with Alzheimer's Disease [J].

Arnold, Steven E. ;

Hyman, Bradley T. ;

Flory, Jill ;

Damasio, Antonio R. ;

Van Hoesen, Gary W. .

CEREBRAL CORTEX, 1991, 1 (01) :103-116

[2] OCCURRENCE OF NEUROPIL THREADS IN THE SENILE HUMAN-BRAIN AND IN ALZHEIMERS-DISEASE - A 3RD LOCATION OF PAIRED HELICAL FILAMENTS OUTSIDE OF NEUROFIBRILLARY TANGLES AND NEURITIC PLAQUES [J].

BRAAK, H ;

BRAAK, E ;

GRUNDKEIQBAL, I ;

IQBAL, K .

NEUROSCIENCE LETTERS, 1986, 65 (03) :351-355

[3] STAGING OF ALZHEIMERS-DISEASE-RELATED NEUROFIBRILLARY CHANGES [J].

BRAAK, H ;

BRAAK, E .

NEUROBIOLOGY OF AGING, 1995, 16 (03) :271-278

[4] Tau protein isoforms, phosphorylation and role in neurodegenerative disorders [J].

Buée, L ;

Bussière, T ;

Buée-Scherrer, V ;

Delacourte, A ;

Hof, PR .

BRAIN RESEARCH REVIEWS, 2000, 33 (01) :95-130

[5] AD2, a phosphorylation-dependent monoclonal antibody directed against tau proteins found in Alzheimer's disease [J].

BueeScherrer, V ;

Condamines, O ;

MourtonGilles, C ;

Jakes, R ;

Goedert, M ;

Pau, B ;

Delacourte, A .

MOLECULAR BRAIN RESEARCH, 1996, 39 (1-2) :79-88

[6] BETA-AMYLOID FIBRILS INDUCE TAU-PHOSPHORYLATION AND LOSS OF MICROTUBULE-BINDING [J].

BUSCIGLIO, J ;

LORENZO, A ;

YEH, J ;

YANKNER, BA .

NEURON, 1995, 14 (04) :879-888

[7] Vulnerable neuronal subsets in Alzheimer's and Pick's disease are distinguished by their τ isoform distribution and phosphorylation [J].

Delacourte, A ;

Sergeant, N ;

Wattez, A ;

Gauvreau, D ;

Robitaille, Y .

ANNALS OF NEUROLOGY, 1998, 43 (02) :193-204

[8] CORRELATIONS OF SYNAPTIC AND PATHOLOGICAL MARKERS WITH COGNITION OF THE ELDERLY [J].

DICKSON, DW ;

CRYSTAL, HA ;

BEVONA, C ;

HONER, W ;

VINCENT, I ;

DAVIES, P .

NEUROBIOLOGY OF AGING, 1995, 16 (03) :285-298

[9]

GALLYAS F, 1971, ACTA MORPHOL HUNG, V19, P1

[10] Aging renders the brain vulnerable to amyloid β-protein neurotoxicity [J].

Geula, C ;

Wu, CK ;

Saroff, D ;

Lorenzo, A ;

Yuan, ML ;

Yankner, BA .

NATURE MEDICINE, 1998, 4 (07) :827-831

← 1 2 3 4 →