Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing a C-terminal fragment of human amyloid precursor protein

Nature ◽  
1991 ◽  
Vol 354 (6353) ◽  
pp. 476-478 ◽  
Author(s):  
Shigeki Kawabata ◽  
Gerald A. Higgins ◽  
Jon W. Gordon
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Neurofibrillary Tangles ◽  
Neuronal Loss ◽  
Amyloid Plaques ◽  
Precursor Protein ◽  
Terminal Fragment

Increased Cystatin C in Astrocytes of Transgenic Mice Expressing the K670N-M671L Mutation of the Amyloid Precursor Protein and Deposition in Brain Amyloid Plaques

2001 ◽  
Vol 8 (4) ◽  
pp. 647-654 ◽  
Author(s):  
Tiana Steinhoff ◽  
Eva Moritz ◽  
M.Axel Wollmer ◽  
M.Hasan Mohajeri ◽  
Stefan Kins ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Cystatin C ◽  
Amyloid Plaques ◽  
Precursor Protein

Transgenic mice expressing the amyloid β protein-containing carboxyl-terminal fragment of the Alzheimer amyloid precursor protein

Amyloid ◽  
1995 ◽  
Vol 2 (2) ◽  
pp. 100-106 ◽  
Author(s):  
Eiichi Araki ◽  
Takeshi Yamada ◽  
Kiyoshi Takemura ◽  
Haruyasu Yamaguchi ◽  
Kenji Sakimura ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Protein ◽  
Terminal Fragment ◽  
Β Protein ◽  
Carboxyl Terminal

Changes in Amyloid-  and Tau in the Cerebrospinal Fluid of Transgenic Mice Overexpressing Amyloid Precursor Protein

2013 ◽  
Vol 5 (194) ◽  
pp. 194re2-194re2 ◽  
Author(s):  
L. F. Maia ◽  
S. A. Kaeser ◽  
J. Reichwald ◽  
M. Hruscha ◽  
P. Martus ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Precursor Protein

scholarly journals Neuroprotective Effects of Asparagus officinalis Stem Extract in Transgenic Mice Overexpressing Amyloid Precursor Protein

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhanglong Peng ◽  
Supinder Bedi ◽  
Vivek Mann ◽  
Alamelu Sundaresan ◽  
Kohei Homma ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Caspase 3 ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Tau Proteins ◽  
Asparagus Officinalis ◽  
Mouse Strains ◽  
Neuroprotective Effects ◽  
Shock Proteins

To mimic Alzheimer’s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.

scholarly journals Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Kreis ◽  
Jana Desloovere ◽  
Nuria Suelves ◽  
Nathalie Pierrot ◽  
Xavier Yerna ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Neuronal Loss ◽  
Gaba Release ◽  
Long Term Potentiation ◽  
Precursor Protein ◽  
Wild Type ◽  
Inhibitory Neurotransmission ◽  
Gaba Production ◽  
Synaptic Functions ◽  
Term Potentiation

AbstractThe function of the amyloid precursor protein (APP) is not fully understood, but its cleavage product amyloid beta (Aβ) together with neurofibrillary tangles constitute the hallmarks of Alzheimer’s disease (AD). Yet, imbalance of excitatory and inhibitory neurotransmission accompanied by loss of synaptic functions, has been reported much earlier and independent of any detectable pathological markers. Recently, soluble APP fragments have been shown to bind to presynaptic GABAB receptors (GABABRs), subsequently decreasing the probability of neurotransmitter release. In this body of work, we were able to show that overexpression of wild-type human APP in mice (hAPPwt) causes early cognitive impairment, neuronal loss, and electrophysiological abnormalities in the absence of amyloid plaques and at very low levels of Aβ. hAPPwt mice exhibited neuronal overexcitation that was evident in EEG and increased long-term potentiation (LTP). Overexpression of hAPPwt did not alter GABAergic/glutamatergic receptor components or GABA production ability. Nonetheless, we detected a decrease of GABA but not glutamate that could be linked to soluble APP fragments, acting on presynaptic GABABRs and subsequently reducing GABA release. By using a specific presynaptic GABABR antagonist, we were able to rescue hyperexcitation in hAPPwt animals. Our results provide evidence that APP plays a crucial role in regulating inhibitory neurotransmission.

scholarly journals Behavioral and Neuropathologic Changes Induced by Central Injection of Carboxyl-Terminal Fragment of β-Amyloid Precursor Protein in Mice

2002 ◽  
Vol 71 (2) ◽  
pp. 875-878 ◽  
Author(s):  
D.-K. Song ◽  
M.-H. Won ◽  
J.-S. Jung ◽  
J.-C. Lee ◽  
T.-C. Kang ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Terminal Fragment ◽  
Β Amyloid ◽  
Carboxyl Terminal
Sign in / Sign up

Export Citation Format

Share Document