Efficient inhibition of beta-secretase gene expression in HEK293 cells by tRNAVal-driven and CTE-helicase associated hammerhead ribozymes.
AuthorsNawrot B, Antoszczyk S, Maszewska M, Kuwabara T, Warashina M, Taira K, Stec WJ,
JournalEur J Biochem
PubMed ID14511378
The beta-amyloid peptide (Abeta) is a major component of toxic amyloid plaques found in the brains of patients with Alzheimer's disease. Abeta is liberated by sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. The level of Abeta depends directly on the hydrolytic activity of beta-secretase. Therefore, beta-secretase ... More
Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease.
AuthorsFagan AM, Watson M, Parsadanian M, Bales KR, Paul SM, Holtzman DM,
JournalNeurobiol Dis
PubMed ID11950276
'The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer''s disease (AD), perhaps through effects on amyloid-beta (Abeta) metabolism. Detailed analyses of various Abeta parameters in aging APP(V717F+/-) transgenic mice expressing mouse apoE, no apoE, or human apoE2, apoE3, or apoE4 demonstrate that apoE facilitates, but is ... More
Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice.
AuthorsDong H, Martin MV, Chambers S, Csernansky JG
JournalJ Comp Neurol
PubMed ID17111375
'Although there is evidence that beta-amyloid impairs synaptic function, the relationship between beta-amyloid and synapse loss is not well understood. In this study we assessed synapse density within the hippocampus and the entorhinal cortex of Tg2576 mice at 6-18 months of age using stereological methods at both the light and ... More
Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation.
AuthorsOakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R
JournalJ Neurosci
PubMed ID17021169
'Mutations in the genes for amyloid precursor protein (APP) and presenilins (PS1, PS2) increase production of beta-amyloid 42 (Abeta42) and cause familial Alzheimer''s disease (FAD). Transgenic mice that express FAD mutant APP and PS1 overproduce Abeta42 and exhibit amyloid plaque pathology similar to that found in AD, but most transgenic ... More
Histamine induces Egr-1 expression in human aortic endothelial cells via the H1 receptor-mediated protein kinase Cdelta-dependent ERK activation pathway.
AuthorsHao F, Tan M, Xu X, Cui MZ
JournalJ Biol Chem
PubMed ID18682391
'Histamine, a potent inflammatory mediator, has multiple effects on the pathogenesis of atherosclerosis. This study investigates the effect of histamine on the expression of early growth response factor 1 (Egr-1), a master transcription factor that regulates the expression of an array of atherogenic genes in atherosclerotic lesions. Histamine markedly and ... More
Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer's disease.
AuthorsHartman RE, Laurer H, Longhi L, Bales KR, Paul SM, McIntosh TK, Holtzman DM,
JournalJ Neurosci
PubMed ID12451108
The epsilon4 allele of apolipoprotein E (APOE) and traumatic brain injury (TBI) are both risk factors for the development of Alzheimer's disease (AD). These factors may act synergistically, in that APOE4+ individuals are more likely to develop dementia after TBI. Because the mechanism underlying these effects is unclear, we questioned ... More
Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease.
AuthorsDeMattos RB, Bales KR, Parsadanian M, O'Dell MA, Foss EM, Paul SM, Holtzman DM,
JournalJ Neurochem
PubMed ID12064470
To better understand amyloid-beta (Abeta) metabolism in vivo, we assessed the concentration of Abeta in the CSF and plasma of APP(V717F) (PDAPP) transgenic mice, a model that develops age-dependent Alzheimer's disease (AD)-like pathology. In 3-month-old mice, prior to the development of Abeta deposition in the brain, there was a highly ... More
Passive immunization against beta-amyloid peptide protects central nervous system (CNS) neurons from increased vulnerability associated with an Alzheimer's disease-causing mutation.
To characterize the effects of the familial Alzheimer's disease-causing Swedish mutations of amyloid precursor protein (SwAPP) on the vulnerability of central nervous system neurons, we induced epileptic seizures in transgenic mice expressing SwAPP. The transgene expression did not change the seizure threshold, but consistently more neurons degenerated in brains of ... More