Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor - PubMed (original) (raw)
. 2004 May 7;279(19):20296-306.
doi: 10.1074/jbc.M312946200. Epub 2004 Feb 25.
Affiliations
- PMID: 14985348
- DOI: 10.1074/jbc.M312946200
Free article
Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor
Judianne Davis et al. J Biol Chem. 2004.
Free article
Abstract
Cerebrovascular deposition of amyloid beta-protein (Abeta) is a common pathological feature of Alzheimer's disease and related disorders. In particular, the Dutch E22Q and Iowa D23N mutations in Abeta cause familial cerebrovascular amyloidosis with abundant diffuse amyloid plaque deposits. Both of these charge-altering mutations enhance the fibrillogenic and pathogenic properties of Abeta in vitro. Here, we describe the generation of several transgenic mouse lines (Tg-SwDI) expressing human neuronal Abeta precursor protein (AbetaPP) harboring the Swedish K670N/M671L and vasculotropic Dutch/Iowa E693Q/D694N mutations under the control of the mouse Thy1.2 promoter. Tg-SwDI mice expressed transgenic human AbetaPP only in the brain, but at levels below those of endogenous mouse AbetaPP. Despite the paucity of human AbetaPP expression, quantitative enzyme-linked immunosorbent assay measurements revealed that Tg-SwDI mice developed early-onset and robust accumulation of Abeta in the brain with high association with isolated cerebral microvessels. Tg-SwDI mice exhibited striking perivascular/vascular Abeta deposits that markedly increased with age. The vascular Abeta accumulations were fibrillar, exhibiting strong thioflavin S staining, and occasionally presented signs of microhemorrhage. In addition, numerous largely diffuse, plaque-like structures were observed starting at 3 months of age. In vivo transport studies demonstrated that Dutch/Iowa mutant Abeta was more readily retained in the brain compared with wild-type Abeta. These results with Tg-SwDI mice demonstrate that overexpression of human AbetaPP is not required for early-onset and robust accumulation of both vascular and parenchymal Abeta in mouse brain.
Similar articles
- Cerebral microvascular amyloid beta protein deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein.
Miao J, Xu F, Davis J, Otte-Höller I, Verbeek MM, Van Nostrand WE. Miao J, et al. Am J Pathol. 2005 Aug;167(2):505-15. doi: 10.1016/s0002-9440(10)62993-8. Am J Pathol. 2005. PMID: 16049335 Free PMC article. - Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid beta-protein precursor transgenic mice.
Xu F, Grande AM, Robinson JK, Previti ML, Vasek M, Davis J, Van Nostrand WE. Xu F, et al. Neuroscience. 2007 Apr 25;146(1):98-107. doi: 10.1016/j.neuroscience.2007.01.043. Epub 2007 Feb 28. Neuroscience. 2007. PMID: 17331655 Free PMC article. - Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice.
Xu F, Vitek MP, Colton CA, Previti ML, Gharkholonarehe N, Davis J, Van Nostrand WE. Xu F, et al. J Neurosci. 2008 May 14;28(20):5312-20. doi: 10.1523/JNEUROSCI.1042-08.2008. J Neurosci. 2008. PMID: 18480287 Free PMC article. - Pathogenic effects of cerebral amyloid angiopathy mutations in the amyloid beta-protein precursor.
Van Nostrand WE, Melchor JP, Romanov G, Zeigler K, Davis J. Van Nostrand WE, et al. Ann N Y Acad Sci. 2002 Nov;977:258-65. doi: 10.1111/j.1749-6632.2002.tb04824.x. Ann N Y Acad Sci. 2002. PMID: 12480759 Review. - Studies on the first described Alzheimer's disease amyloid beta mutant, the Dutch variant.
Levy E, Prelli F, Frangione B. Levy E, et al. J Alzheimers Dis. 2006;9(3 Suppl):329-39. doi: 10.3233/jad-2006-9s337. J Alzheimers Dis. 2006. PMID: 16914871 Review.
Cited by
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.
Stevenson M, Algarzae NK, Moussa C. Stevenson M, et al. Front Dement. 2024 Aug 16;3:1458038. doi: 10.3389/frdem.2024.1458038. eCollection 2024. Front Dement. 2024. PMID: 39221072 Free PMC article. Review. - Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies.
van Veluw SJ, Benveniste H, Bakker ENTP, Carare RO, Greenberg SM, Iliff JJ, Lorthois S, Van Nostrand WE, Petzold GC, Shih AY, van Osch MJP. van Veluw SJ, et al. Cell Mol Life Sci. 2024 May 27;81(1):239. doi: 10.1007/s00018-024-05277-1. Cell Mol Life Sci. 2024. PMID: 38801464 Free PMC article. Review. - A Combination of Heavy Metals and Intracellular Pathway Modulators Induces Alzheimer Disease-like Pathologies in Organotypic Brain Slices.
Korde DS, Humpel C. Korde DS, et al. Biomolecules. 2024 Jan 30;14(2):165. doi: 10.3390/biom14020165. Biomolecules. 2024. PMID: 38397402 Free PMC article. - Behavioral and Neuronal Characterizations, across Ages, of the TgSwDI Mouse Model of Alzheimer's Disease.
Tan NA, Carpio AMA, Heller HC, Pittaras EC. Tan NA, et al. Genes (Basel). 2023 Dec 28;15(1):47. doi: 10.3390/genes15010047. Genes (Basel). 2023. PMID: 38254938 Free PMC article. - Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy.
Platholi J, Marongiu R, Park L, Yu F, Sommer G, Weinberger R, Tower W, Milner TA, Glass MJ. Platholi J, et al. Front Aging Neurosci. 2023 Nov 15;15:1280218. doi: 10.3389/fnagi.2023.1280218. eCollection 2023. Front Aging Neurosci. 2023. PMID: 38035277 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous