Rapid detection of protein aggregates in the brains of Alzheimer patients and transgenic mouse models of amyloidosis

作者: Guilian Xu , Victoria Gonzales , David R. Borchelt

DOI: 10.1097/00002093-200207000-00010

关键词: ExtracellularProtein aggregationImmunostainingTau proteinAmyloidosisAlzheimer's diseaseIntracellularGenetically modified mouseBiologyCell biologyPathology

摘要: Extracellular and/or intracellular aggregates are pathological features of many, if not all, neurodegenerative diseases. In Alzheimer disease (AD), extracellular beta-amyloid (Abeta) and tau or a-synuclein key diagnostic markers the disease. We report here a method to rapidly detect these protein that relies on size exclusion filtration immunostaining trapped material, termed filter trapping. demonstrate aggregated forms Abeta readily in 0.22 microm cellulose acetate membranes, which can then be immunostained with specific antibodies manner similar standard immunoblot. Coupling this serial dilution permits rapid assessment relative aggregate burden.

参考文章(13)
H.H. Slunt, G. Thinakaran, C. Von Koch, A.C. Lo, R.E. Tanzi, S.S. Sisodia, Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). Journal of Biological Chemistry. ,vol. 269, pp. 2637- 2644 ,(1994) , 10.1016/S0021-9258(17)41992-2
Joanna L Jankowsky, Hilda H Slunt, Tamara Ratovitski, Nancy A Jenkins, Neal G Copeland, David R Borchelt, Co-expression of multiple transgenes in mouse CNS: a comparison of strategies Biomolecular Engineering. ,vol. 17, pp. 157- 165 ,(2001) , 10.1016/S1389-0344(01)00067-3
Donald L Price, Sangram S Sisodia, David R Borchelt, None, Genetic Neurodegenerative Diseases: The Human Illness and Transgenic Models Science. ,vol. 282, pp. 1079- 1083 ,(1998) , 10.1126/SCIENCE.282.5391.1079
Robert D. Terry, Robert Katzman Katzman, Senile dementia of the Alzheimer type. Annals of Neurology. ,vol. 14, pp. 497- 506 ,(1983) , 10.1002/ANA.410140502
David R Borchelt, Michael K Lee, Victoria Gonzales, Hilda H Slunt, Tamara Ratovitski, Nancy A Jenkins, Neal G Copeland, Donald L Price, Sangram S Sisodia, None, Accumulation of proteolytic fragments of mutant presenilin 1 and accelerated amyloid deposition are co-regulated in transgenic mice Neurobiology of Aging. ,vol. 23, pp. 171- 177 ,(2002) , 10.1016/S0197-4580(01)00280-9
E. Scherzinger, A. Sittler, K. Schweiger, V. Heiser, R. Lurz, R. Hasenbank, G. P. Bates, H. Lehrach, E. E. Wanker, Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington’s disease pathology Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 4604- 4609 ,(1999) , 10.1073/PNAS.96.8.4604
David R Borchelt, Tamara Ratovitski, Judy Van Lare, Michael K Lee, Vicki Gonzales, Nancy A Jenkins, Neal G Copeland, Donald L Price, Sangram S Sisodia, None, Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins Neuron. ,vol. 19, pp. 939- 945 ,(1997) , 10.1016/S0896-6273(00)80974-5
Eberhard Scherzinger, Rudi Lurz, Mark Turmaine, Laura Mangiarini, Birgit Hollenbach, Renate Hasenbank, Gillian P Bates, Stephen W Davies, Hans Lehrach, Erich E Wanker, Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo Cell. ,vol. 90, pp. 549- 558 ,(1997) , 10.1016/S0092-8674(00)80514-0
David R Borchelt, Janine Davis, Marek Fischer, Micheal K Lee, Hilda H Slunt, Tamara Ratovitsky, Jean Regard, Neal G Copeland, Nancy A Jenkins, Sangram S Sisodia, Donald L Price, None, A vector for expressing foreign genes in the brains and hearts of transgenic mice Genetic Analysis: Biomolecular Engineering. ,vol. 13, pp. 159- 163 ,(1996) , 10.1016/S1050-3862(96)00167-2
Michael K Lee, David R Borchelt, Grace Kim, Gopal Thinakaran, Hilda H Slunt, Tamara Ratovitski, Lee J Martin, Anik Kittur, Samuel Gandy, Allan I Levey, Nancy Jenkins, Neal Copeland, Donald L Price, Sangram S Sisodia, None, HYPERACCUMULATION OF FAD-LINKED PRESENILIN 1 VARIANTS IN VIVO Nature Medicine. ,vol. 3, pp. 756- 760 ,(1997) , 10.1038/NM0797-756