Title |
BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions
|
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Published in |
The Journal of Experimental Medicine, February 2018
|
DOI | 10.1084/jem.20171831 |
Pubmed ID | |
Authors |
Xiangyou Hu, Brati Das, Hailong Hou, Wanxia He, Riqiang Yan |
Abstract |
BACE1 initiates the generation of the β-amyloid peptide, which likely causes Alzheimer's disease (AD) when accumulated abnormally. BACE1 inhibitory drugs are currently being developed to treat AD patients. To mimic BACE1 inhibition in adults, we generated BACE1 conditional knockout (BACE1fl/fl) mice and bred BACE1fl/flmice with ubiquitin-CreERmice to induce deletion of BACE1 after passing early developmental stages. Strikingly, sequential and increased deletion of BACE1 in an adult AD mouse model (5xFAD) was capable of completely reversing amyloid deposition. This reversal in amyloid deposition also resulted in significant improvement in gliosis and neuritic dystrophy. Moreover, synaptic functions, as determined by long-term potentiation and contextual fear conditioning experiments, were significantly improved, correlating with the reversal of amyloid plaques. Our results demonstrate that sustained and increasing BACE1 inhibition in adults can reverse amyloid deposition in an AD mouse model, and this observation will help to provide guidance for the proper use of BACE1 inhibitors in human patients. |
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Geographical breakdown
Country | Count | As % |
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United States | 42 | 22% |
United Kingdom | 10 | 5% |
France | 6 | 3% |
India | 5 | 3% |
Spain | 4 | 2% |
Canada | 4 | 2% |
Brazil | 3 | 2% |
Saudi Arabia | 3 | 2% |
South Africa | 2 | 1% |
Other | 28 | 15% |
Unknown | 83 | 44% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 150 | 79% |
Scientists | 29 | 15% |
Science communicators (journalists, bloggers, editors) | 7 | 4% |
Practitioners (doctors, other healthcare professionals) | 4 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 188 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 35 | 19% |
Student > Ph. D. Student | 28 | 15% |
Student > Bachelor | 28 | 15% |
Student > Master | 25 | 13% |
Student > Postgraduate | 10 | 5% |
Other | 25 | 13% |
Unknown | 37 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 36 | 19% |
Biochemistry, Genetics and Molecular Biology | 33 | 18% |
Agricultural and Biological Sciences | 22 | 12% |
Medicine and Dentistry | 17 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 4% |
Other | 30 | 16% |
Unknown | 43 | 23% |