Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw

Hwang, Dae Youn; Cho, Jung S.; Lee, Su H.; Chae, Kab Ryong; Lim, Hwa J.; Min, Sea H.; Seo, Su J.; Song, Youn S.; Song, Chang‐Hwa; Paik, Sang Gi; Sheen, Yhun Yhong; Kim, Yong K.

doi:10.1016/j.expneurol.2003.09.021

Cited by 62 publications

(54 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, overexpression generates vast amounts of protein that could enable an unrepresentative large detectable reduction in protein levels in intervention studies. Furthermore, the Tg NSE/APPsw mouse model used by Um et al [12] does not develop plaques, as seen in human patients with AD [36]. The abovementioned concern suggests that the different pathology of Aβ in the mouse makes direct comparison of the effect of an exercise intervention between humans and animal models less valid and could account for the disagreement between our findings and previous animal findings.…”

Section: Discussioncontrasting

confidence: 57%

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

Jensen

Portelius

Siersma

et al. 2016

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background: Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aβ), one of the pathological hallmarks of AD, can be altered with high levels of physical activity. Aim: The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway. Methods: From a total of 53 patients with AD participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study we analyzed cerebrospinal fluid samples for Aβ species, total tau (t-tau), phosphorylated tau (p-tau) and soluble amyloid precursor protein (sAPP) species. We also assessed the patients for apolipoprotein E ε4 (ApoE ε4) genotype. Results: We found no effect of 16 weeks of physical exercise on the selected biomarkers, and no effect of ApoE ε4 genotype. Conclusion: Our findings suggest that the possible effect of physical exercise on cognition in patients with AD is not due to modulation of Aβ, t-tau, p-tau and sAPP species.

show abstract

Section: Discussioncontrasting

confidence: 57%

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

Jensen

Portelius

Siersma

et al. 2016

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…There is considerable evidence that one mechanism by which neurons die in AD is apoptosis (for review, see LeBlanc, 2005). Indeed, several groups have reported the presence of activated caspases in the postmortem brains of individuals with AD (Selznick et al, 1999;Stadelmann et al, 1999;Raina et al, 2001) and have described apoptotic neurons in the brains of transgenic mouse models for AD (LaFerla et al, 1995;Chui et al, 1999;Xie et al, 2001;Hwang et al, 2004). We showed previously that exogenous expression of FAD APP mutations or of APP-BP1 in primary neurons causes cell cycle entry followed by apoptosis (McPhie et al, 1997(McPhie et al, , 2001).…”

Section: Discussionmentioning

confidence: 99%

Rab5 Mediates an Amyloid Precursor Protein Signaling Pathway That Leads to Apoptosis

Laifenfeld¹,

Patzek²,

McPhie³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Alzheimer's disease (AD) involves activation of apoptotic pathways that may be regulated through signaling cascades initiated by the amyloid precursor protein (APP). Enlarged endosomes have been observed in postmortem AD brains at very early stages of the disease. We show here that exogenous expression of a familial AD (FAD) mutant of APP or of the APP binding protein APP-BP1 in neurons causes enlargement of early endosomes, increased receptor-mediated endocytosis via a pathway dependent on APP-BP1 binding to APP, and apoptosis. Levels of both APP-BP1 and Rab5 are elevated in early endosomes in cortical embryonic neurons expressing APP(V642I) or APP-BP1, in cultured skin fibroblast cells from Down syndrome subjects, and in postmortem hippocampal tissue of individuals with AD. Indeed, Rab5 was found to bind specifically to APP-BP1, between amino acids 443 and 479. Inhibition of Rab5 or dynamin activity, but not of Eps15 (epidermal growth factor receptor pathway substrate 15) activity, rescued neurons from apoptosis induced by either APP(V642I) or APP-BP1, without affecting levels of intracellular or secreted amyloid-␤ (A␤). Induction of Rab5 activity via expression of a constitutively active mutant led to an increase in neuronal apoptosis more than twice that attributable to induction of endosome enlargement via a Rab5-independent mechanism, regardless of A␤ production. Together, these findings suggest that Rab5 activation via an APP/APP-BP1-initiated signaling pathway mediates neuronal apoptosis caused by FAD mutants of APP and that, within this pathway, Rab5 has a specific role in signaling that is distinct from, although not independent of, its role in trafficking.

show abstract

“…NSE/APPsw Tg mice expressing the human APPsw gene under the control of the neuron-specific enolase (NSE) promoter were used for this study. These mice present AD phenotypes, including behavioral dysfunction, Aß-42 deposition and apoptosis activation at 12-13 months of age (23). The Non-Tg and Tg mice were obtained from the Department of Laboratory Animal Resources at the National Institute of Toxicological Research, Korea FDA.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analyses were conducted as previously described (23). Briefly, proteins (40 μg) were separated by electrophoresis on a 10% polyacrylamide gel for 3 h, after which they were transferred to a nitrocellulose membrane (Immuno-Blot, PVDF membrane, Bio-Rad, CA, USA) for 2 h at a constant voltage of 40 volts.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have demonstrated that the APPsw Tg mice used in this study exhibit behavioral deficits at 13 months of age, and that these deficits are accompanied by increased levels of Aß-42 (23). Therefore, the initial purpose of the study was to estimate whether treatment with ET alone, LA alone or COMA affected the behavioral dysfunction of AD pheno-types.…”

Section: Preventative Effects Of Exercise Training and ·-Lipoic Acid mentioning

confidence: 99%

See 1 more Smart Citation

The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

Cho¹

2010

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Exercise training was suggested as a practical therapeutic strategy for human subjects suffering from Alzheimer's disease (AD) in our previous study. Therefore, the purpose of this study was to investigate the effects of combining exercise training with the administration of antioxidants on the pathological phenotype of AD. To accomplish this, non-transgenic mice (Non-Tg) and NSE/ APPsw Tg mice were treated with ·-lipoic acid and treadmill exercised for 16 weeks, after which their brains were evaluated to determine whether any changes in the pathological phenotype-related factors occurred. The results indicated that (i) the combination-applied (COMA) Tg group with exercise training (ET) and ·-lipoic acid administration (LA) showed ameliorated spatial learning and memory compared to the sedentary (SED)-Tg and single-treatment groups; (ii) there were no differences in the level of Aß-42 peptides across groups; (iii) the level of glucose transporter-1 and brain-derived neurotrophic factor proteins were highly increased in the COMA group, (iv) ET and LA did not induce a synergistic effect on the expression of heat shock protein-70 and apoptotic proteins including Bax and caspase-3; (v) the levels of SOD-1 and CAT suppressing oxidative stress were extensively higher in the COMA than in the singletreated groups and (vi) there were no significant differences across groups regarding these serum characteristics, although these levels were lower than the SED-Tg group. Taken together, these results suggest that the combination with ET and LA may contribute to protect the neuron injury induced by Aß peptides and may be considered an effective therapeutic strategy for human subjects suffering from AD.

show abstract

Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw

Cited by 62 publications

References 64 publications

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease

Rab5 Mediates an Amyloid Precursor Protein Signaling Pathway That Leads to Apoptosis

The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

Contact Info

Product

Resources

About