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APP Expression (app + expression)
Selected AbstractsAPP is required during an early phase of memory formationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000R. Mileusnic Abstract The amyloid ,/A4 protein precursor (APP) has been shown to be implicated in age-associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, we have employed a one-trial passive avoidance task in day-old chicks to study its role in the process of memory formation. Administration of anti-APP antibodies, injected 30 min pretraining, prevented memory for a one-trial passive avoidance task in day-old chicks without effects on general behaviour or initial acquisition. Amnesia was apparent by 30 min post-training and lasted for at least 24 h. The same result was obtained by down-regulation of APP expression by APP-antisense, injected 8,12 h pretraining. However, injections of anti-APP antibodies or APP antisense at later post-training time did not cause amnesia for the task. Unlike antibodies and antisense, injection of the APP328,332 pentapeptide, in either orientation, 30 min pretraining, rescued the memory and prevented antisense-induced amnesia. The post-training time within which the antibody- and antisense-induced amnesia, and within which the APP peptides prevent amnesia, correspond to that during which memory formation is vulnerable to disruption of the putative signal transduction functions of APP. These results suggest that: (i) APP is required during an early phase of memory formation, and (ii) the memory enhancing effect of secretory APP is localized within a 5-mer sequence of growth-promoting domain. [source] BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild-type mice,JOURNAL OF NEUROCHEMISTRY, Issue 6 2006Kouhei Nishitomi Abstract Accumulation of amyloid beta peptide (Abeta) in brain is a hallmark of Alzheimer's disease (AD). Inhibition of beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE1), the enzyme that initiates Abeta production, and other Abeta-lowering strategies are commonly tested in transgenic mice overexpressing mutant APP. However, sporadic AD cases, which represent the majority of AD patients, are free from the mutation and do not necessarily have overproduction of APP. In addition, the commonly used Swedish mutant APP alters APP cleavage. Therefore, testing Abeta-lowering strategies in transgenic mice may not be optimal. In this study, we investigated the impact of BACE1 inhibition in non-transgenic mice with physiologically relevant APP expression. Existing Abeta ELISAs are either relatively insensitive to mouse Abeta or not specific to full-length Abeta. A newly developed ELISA detected a significant reduction of full-length soluble Abeta 1,40 in mice with the BACE1 homozygous gene deletion or BACE1 inhibitor treatment, while the level of x-40 Abeta was moderately reduced due to detection of non-full-length Abeta and compensatory activation of alpha-secretase. These results confirmed the feasibility of Abeta reduction through BACE1 inhibition under physiological conditions. Studies using our new ELISA in non-transgenic mice provide more accurate evaluation of Abeta-reducing strategies than was previously feasible. [source] Potential roles of Alzheimer precursor protein A4 and ,-amyloid in survival and function of aged spinal motor neurons after axonal injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Yuanyun Xie Abstract To study the potential role of Alzheimer precursor protein A4 (APP) and ,-amyloid (A/,) on aging motor neuron survival, expression of APP, A/,, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP-positive. A/,-positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT-immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post-injury. In contrast, after avulsion, expression of APP and A/, were downregulated in the spinal ventral horn of aged rats, and marked loss of spinal motor neurons and downregulated ChaT expression were observed. Our data indicate that APP and A/, might play beneficial roles in neuronal survival of aged spinal motor neurons after axonal injury. © 2003 Wiley-Liss, Inc. [source] Intraneuronal APP/A, Trafficking and Plaque Formation in ,-Amyloid Precursor Protein and Presenilin-1 Transgenic MiceBRAIN PATHOLOGY, Issue 3 2002Oliver Wirths Neuropil deposition of ,-amyloid peptides A,40 and A,42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since A, seems to carry a transport signal that is required for axonal sorting of its precursor ,-amyloid precursor protein (APP), we studied the intraneuronal staining profile of A, peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L) in neurons. Using surface plasmon resonance we analyzed the A, antibodies and defined their binding profile to APP, A,40 and A,42. Immunohistochemical staining revealed that intraneuronal A,40 and A,42 staining preceded plaque deposition, which started at 3 months of age. A, was observed in the somatodendritic and axonal compartments of many neurons. Interestingly, the striatum, which lacks transgenic APP expression harbored many plaques at 10 months of age. This is most likely due to an APP/A, transport problem and may be a model region to study APP/A, trafficking as an early pathological event. [source] | ||||||||||