1,979 results match your criteria app-ps1 mice

Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology.

Aging Cell 2021 Jun 12:e13416. Epub 2021 Jun 12.

Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. Read More

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Photoactivation of TGFβ/SMAD signaling pathway ameliorates adult hippocampal neurogenesis in Alzheimer's disease model.

Stem Cell Res Ther 2021 Jun 11;12(1):345. Epub 2021 Jun 11.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.

Background: Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer's disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved.

Methods: Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0. Read More

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Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer's disease.

Commun Biol 2021 Jun 10;4(1):711. Epub 2021 Jun 10.

Trinity College Institute for Neuroscience, Trinity College, Dublin 2, Ireland.

Age and sex are major risk factors in Alzheimer's disease (AD) with a higher incidence of the disease in females. Neuroinflammation, which is a hallmark of AD, contributes to disease pathogenesis and is inexorably linked with inappropriate microglial activation and neurodegeneration. We investigated sex-related differences in microglia in APP/PS1 mice and in post-mortem tissue from AD patients. Read More

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Exploring the microbiota-Alzheimer's Disease linkage using short-term antibiotic treatment followed by fecal microbiota transplantation.

Brain Behav Immun 2021 Jun 7. Epub 2021 Jun 7.

School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510641, China; Sino-Singapore International Joint Research Institute, Guangzhou Knowledge City, Guangzhou, Guangdong 510555, China. Electronic address:

Gut microbiota is proven to be involved in the development of beta amyloid (Aβ) pathology in Alzheimer's disease (AD). Since there are difficulties in translating microbiota findings based on germ-free mice into clinical practice, here, we used short-term antibiotic cocktail treatment to develop a novel model with a near-germ-free status and without impacting Aβ pathology. Three months old APP/PS1 mice were fed with antibiotic cocktails for two weeks by gavage to obtain a near "germ-free" status, and then received the donor fecal matter from the 16 months old APP/PS1 mice for 7 consecutive days. Read More

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Formulated Chinese medicine Shaoyao Gancao Tang reduces NLRP1 and NLRP3 in Alzheimer's disease cell and mouse models for neuroprotection and cognitive improvement.

Aging (Albany NY) 2021 Jun 9;13. Epub 2021 Jun 9.

Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.

Amyloid β (Aβ) plays a major role in the neurodegeneration of Alzheimer's disease (AD). The accumulation of misfolded Aβ causes oxidative stress and inflammatory damage leading to apoptotic cell death. Traditional Chinese herbal medicine (CHM) has been widely used in treating neurodegenerative diseases by reducing oxidative stress and neuroinflammation. Read More

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Tetramethylpyrazine Improves Cognitive Function of Alzheimer's Disease Mice by Regulating SSTR4 Ubiquitination.

Drug Des Devel Ther 2021 1;15:2385-2399. Epub 2021 Jun 1.

Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, People's Republic of China.

Purpose: Many researches have investigated the functions of tetramethylpyrazine (TMP) in Alzheimer's disease (AD). This study aimed to discuss the underlying mechanism of TMP in AD mice.

Methods: TMP (200 mg/kg) was administered to 6-month-old APP/PS1 transgenic mice, and behavioral changes and hippocampal nerve injury in AD mice were detected. Read More

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Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease.

Neuron 2021 Jun 3. Epub 2021 Jun 3.

Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China. Electronic address:

Severe cognitive decline is a hallmark of Alzheimer's disease (AD). In addition to gray matter loss, significant white matter pathology has been identified in AD patients. Here, we characterized the dynamics of myelin generation and loss in the APP/PS1 mouse model of AD. Read More

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Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer's disease.

Eur J Med Chem 2021 May 29;222:113554. Epub 2021 May 29.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, People's Republic of China. Electronic address:

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss and behavioral disturbances, ultimately leading to death. Glycogen synthase kinase 3β (GSK-3β) and dual-specificity tyrosine phosphorylation regulated kinase1A (DYRK1A) have gained a lot of attention for its role in tau pathology. To search for potential dual GSK-3β/DYRK1A inhibitors, we focused on harmine, a natural β-carboline alkaloid, which has been extensively studied for its various biological effects on the prevention of AD. Read More

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Interaction between extracellular ATP5A1 and LPS alleviates LPS-induced neuroinflammation in mice.

Neurosci Lett 2021 Jun 4:136005. Epub 2021 Jun 4.

Department of Translational Neuroscience, Jing'an District Centre Hospital of shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi-Xue-Yuan Road, Shanghai 200032, China. Electronic address:

Neuroinflammation is one of the main causes of Alzheimer's disease (AD). The presence of Lipopolysaccharide (LPS) in senile plaques (SP) of AD suggests that it plays a role in AD pathogenesis. ATP5A1 (F1F0-ATP synthase F1 α subunit) is abundant in SP. Read More

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ARCAM-1 Facilitates Fluorescence Detection of Amyloid-Containing Deposits in the Retina.

Transl Vis Sci Technol 2021 Jun;10(7)

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.

Purpose: To investigate the use of an amyloid-targeting fluorescent probe, ARCAM-1, to identify amyloid-containing deposits in the retina of a transgenic mouse model of Alzheimer's disease (AD) and in human postmortem AD patients.

Methods: Aged APP/PS1 transgenic AD and wild-type (WT) mice were given an intraperitoneal (IP) injection of ARCAM-1 and their retinas imaged in vivo using a fluorescence ophthalmoscope. Eyes were enucleated and dissected for ex vivo inspection of retinal amyloid deposits. Read More

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CircRNA-ceRNA Network Revealing the Potential Regulatory Roles of CircRNA in Alzheimer's Disease Involved the cGMP-PKG Signal Pathway.

Front Mol Neurosci 2021 21;14:665788. Epub 2021 May 21.

Institute of Biomedical Research, School for Life Sciences, Shandong University of Technology, Zibo, China.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease. The characteristic pathologies include extracellular senile plaques formed by β-amyloid protein deposition, neurofibrillary tangles formed by hyperphosphorylation of tau protein, and neuronal loss with glial cell hyperplasia. Circular RNAs (circRNAs) are rich in miRNA-binding sites (miRNA response elements, MREs), which serve as miRNA sponges or competitive endogenous RNAs (ceRNAs). Read More

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Chronic sleep deprivation exacerbates cognitive and synaptic plasticity impairments in APP/PS1 transgenic mice.

Behav Brain Res 2021 Jun 2;412:113400. Epub 2021 Jun 2.

Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits. Sleep deprivation (SD) could lead to memory deficits, and it was a candidate risk factor for AD. However, the effects of chronic SD on the cognitive functions of AD model mice and its possible mechanism are still unclear. Read More

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Shenzhiling oral liquid protects the myelin sheath against Alzheimer's disease through the PI3K/Akt-mTOR pathway.

J Ethnopharmacol 2021 Jun 1;278:114264. Epub 2021 Jun 1.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, 100700, China; Key Laboratory of Pharmacology Dongzhimen Hospital (BUCM), State Administration of Traditional Chinese Medicine, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: Shenzhiling oral liquid (SZL), a traditional Chinese medicine (TCM) compound, is firstly approved by the Chinese Food and Drug Administration (CFDA) for the treatment of mild to moderate Alzheimer's disease (AD). SZL is composed of ten Chinese herbs, and the precise therapy mechanism of its action to AD is far from fully understood.

Aim Of The Study: The purpose of this study was to observe whether SZL is an effective therapy for amyloid-beta (Aβ)-induced myelin sheath and oligodendrocytes impairments. Read More

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Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1β drives amplified responses in primed astrocytes and neuronal network dysfunction.

Alzheimers Dement 2021 Jun 3. Epub 2021 Jun 3.

School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Rep. of Ireland.

Neuroinflammation contributes to Alzheimer's disease (AD) progression. Secondary inflammatory insults trigger delirium and can accelerate cognitive decline. Individual cellular contributors to this vulnerability require elucidation. Read More

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The Density of Group I mGlu Receptors Is Reduced along the Neuronal Surface of Hippocampal Cells in a Mouse Model of Alzheimer's Disease.

Int J Mol Sci 2021 May 30;22(11). Epub 2021 May 30.

Synaptic Structure Laboratory, Instituto de Investigación en Discapacidades Neurológicas (IDINE), Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Campus Biosanitario, C/Almansa 14, 02006 Albacete, Spain.

Metabotropic glutamate receptor subtype 5 (mGlu) is implicated in the pathophysiology of Alzheimer´s disease (AD). However, its alteration at the subcellular level in neurons is still unexplored. Here, we provide a quantitative description on the expression and localisation patterns of mGlu in the APP/PS1 model of AD at 12 months of age, combining immunoblots, histoblots and high-resolution immunoelectron microscopic approaches. Read More

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Longitudinal Assessment of Working Memory Performance in the APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease Using an Automated Figure-8-Maze.

Front Behav Neurosci 2021 13;15:655449. Epub 2021 May 13.

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with a long preclinical and prodromal phase. To enable the study of disease mechanisms, AD has been modeled in many transgenic animal lines and cognitive functioning has been tested using several widely used behavioral tasks. These tasks, however, are not always suited for repeated longitudinal testing and are often associated with acute stress such as animal transfer, handling, novelty, or stress related to the task itself. Read More

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Anti-LINGO-1 antibody ameliorates cognitive impairment, promotes adult hippocampal neurogenesis, and increases the abundance of CB1R-rich CCK-GABAergic interneurons in AD mice.

Neurobiol Dis 2021 May 24;156:105406. Epub 2021 May 24.

Department of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, PR China; Laboratory of Stem Cell and Tissue Engineering, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, PR China. Electronic address:

In view of the negative regulatory effect of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) on neurons, an antibody against LINGO-1 (anti-LINGO-1 antibody) was herein administered to 10-month-old APP/PS1 transgenic Alzheimer's disease (AD) mice for 2 months as an experimental intervention. Behavioral, stereology, immunohistochemistry and immunofluorescence analyses revealed that the anti-LINGO-1 antibody significantly improved the cognitive abilities, promoted adult hippocampal neurogenesis (AHN), decreased the amyloid beta (Aβ) deposition, enlarged the hippocampal volume, and increased the numbers of total neurons and GABAergic interneurons, including GABAergic and CCK-GABAergic interneurons rich in cannabinoid type 1 receptor (CB1R), in the hippocampus of AD mice. In contrast, this intervention significantly reduced the number of GABAergic interneurons expressing LINGO-1 and CB1R in the hippocampus of AD mice. Read More

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Progesterone Suppresses Cholesterol Esterification in APP/PS1 mice and a cell model of Alzheimer's Disease.

Brain Res Bull 2021 Aug 25;173:162-173. Epub 2021 May 25.

Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China; Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang 050082, Hebei Province, China. Electronic address:

Aims: Cholesteryl ester(CE), generated from the mitochondria associated membrane (MAM), is involved in the pathogenesis of Alzheimer's Disease (AD). In theory, the different neuroprotective effects of progesterone in AD are all linked to MAM, yet the effect on cholesterol esterification has not been reported. Therefore, this study was aimed to investigate the regulation of progesterone on intracerebral CE in AD models and the underlying mechanism. Read More

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Brain Targeting and Aβ Binding Bifunctional Nanoparticles Inhibit Amyloid Protein Aggregation in APP/PS1 Transgenic Mice.

ACS Chem Neurosci 2021 May 27. Epub 2021 May 27.

College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disease with few disease-modifying treatments. A variety of peptide/protein drugs have neuroprotective effects, which brings new hope for the treatment of AD. However, the application of these drugs is limited because of their low specificity and difficulty in crossing the blood-brain barrier. Read More

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κ‑opioid receptor agonist, U50488H, inhibits pyroptosis through NLRP3 via the Ca/CaMKII/CREB signaling pathway and improves synaptic plasticity in APP/PS1 mice.

Mol Med Rep 2021 Jul 26;24(1). Epub 2021 May 26.

Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder with slow onset in most cases. Clinically, dementia associated with AD is characterized by memory disorders, aphasia, executive dysfunction and personality and behavior changes. Currently, treatment strategies attempt to reduce certain symptoms, however there is no cure for AD. Read More

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Long-Term Administration of Triterpenoids From Mitigates Age-Associated Brain Physiological Decline via Regulating Sphingolipid Metabolism and Enhancing Autophagy in Mice.

Front Aging Neurosci 2021 6;13:628860. Epub 2021 May 6.

State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

With the advent of the aging society, how to grow old healthily has become an important issue for the whole of society. Effective intervention strategies for healthy aging are most desired, due to the complexity and diversity of genetic information, it is a pressing concern to find a single drug or treatment to improve longevity. In this study, long-term administration of triterpenoids of (TGL) can mitigate brain physiological decline in normal aging mice. Read More

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Changes in Biothiol Levels Are Closely Associated with Alzheimer's Disease.

J Alzheimers Dis 2021 May 19. Epub 2021 May 19.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China.

Background: Serum homocysteine (Hcy) level is considered to be an important biomarker for Alzheimer's disease (AD); however, the status of Hcy in brain tissue, and the association between brain and serum levels of Hcy in AD patients remain unclear.

Objective: We aimed to examine whether the changes of three thiols are consistent in serum of AD patients and the brain of APP/PS1 mice, and to verify the effectiveness of Hcy as a biomarker for early AD detection.

Methods: The levels of Hcy, cysteine (Cys), and glutathione (GSH) in Aβ 1-42-treated PC12 cells, the brain and hippocampus of APP/PS1 mouse, and the serum of AD patients were evaluated using ethyl (E)-3-(9-chloro-11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f] pyrido [3,2,1 -ij] quinolin-10-yl)-2-cyanoacrylate (Probe 1) and ELISA assay or LC-MS. Read More

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Bilobalide alleviates neuroinflammation and promotes autophagy in Alzheimer's disease by upregulating lincRNA-p21.

Am J Transl Res 2021 15;13(4):2021-2040. Epub 2021 Apr 15.

Department of Neurology, The First Affiliated Hospital of Soochow University Suzhou 215006, China.

EGb 761 has some protective effects on AD and can improve the cognitive functions of AD mice. However, the underlying molecular mechanisms are unknown. Here, we investigated the function of bilobalide, the effective component of EGb 761, in neuroinflammation and autophagy during AD. Read More

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Post-transcriptional regulation of α7 nAChR expression by miR-98-5p modulates cognition and neuroinflammation in an animal model of Alzheimer's disease.

FASEB J 2021 Jun;35(6):e21658

Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Alzheimer's disease (AD) is a complicated neurodegenerative disease and therefore addressing multiple targets simultaneously has been believed as a promising therapeutic strategy against AD. α7 nicotinic acetylcholine receptor (nAChR), which plays an important role in improving cognitive function and alleviating neuroinflammation in central nervous system (CNS), has been regarded as a potential target in the treatment of AD. However, the regulation of α7 nAChR at post-transcriptional level in mammalian brain remains largely speculated. Read More

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Rapamycin activates mitophagy and alleviates cognitive and synaptic plasticity deficits in a mouse model of Alzheimer's disease.

J Gerontol A Biol Sci Med Sci 2021 May 18. Epub 2021 May 18.

College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, PR China.

Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is characterized by cognitive and synaptic plasticity damage. Rapamycin is an activator of autophagy/mitophagy, which plays an important role in identifying and degrading damaged mitochondria. The aim of this study was to investigate the effect of rapamycin on cognitive and synaptic plasticity defects induced by AD, and further explore if the underlying mechanism was associated with mitophagy. Read More

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TRPV1 sustains microglial metabolic reprogramming in Alzheimer's disease.

EMBO Rep 2021 Jun 17;22(6):e52013. Epub 2021 May 17.

Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

As the brain-resident innate immune cells, reactive microglia are a major pathological feature of Alzheimer's disease (AD). However, the exact role of microglia is still unclear in AD pathogenesis. Here, using metabolic profiling, we show that microglia energy metabolism is significantly suppressed during chronic Aβ-tolerant processes including oxidative phosphorylation and aerobic glycolysis via the mTOR-AKT-HIF-1α pathway. Read More

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Long-Term Consequence of Non-neurotropic H3N2 Influenza A Virus Infection for the Progression of Alzheimer's Disease Symptoms.

Front Cell Neurosci 2021 28;15:643650. Epub 2021 Apr 28.

Department of Cellular Neurobiology, Zoological Institute, TU-Braunschweig, Braunschweig, Germany.

Influenza viruses until today are a leading cause of worldwide severe pandemics and represent a major threat to human and animal health. Although the primary target of influenza viruses is the lung, infection may manifest with acute and even chronic neurological complications (e.g. Read More

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HnRNP F and hnRNP H1 regulate mRNA stability of amyloid precursor protein.

Neuroreport 2021 Jun;32(9):824-832

Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences.

Amyloid precursor protein (APP) is a transmembrane protein that plays a crucial role in the production of amyloid-β peptides. Any disruption in APP protein production, its mRNA decay rate or processing may result in abnormal production of amyloid-β peptides and subsequent development of protein aggregation diseases. Therefore, the equilibrium is crucial for neuronal function. Read More

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Plasmalogen attenuates the development of hepatic steatosis and cognitive deficit through mechanism involving p75NTR inhibition.

Redox Biol 2021 Jul 7;43:102002. Epub 2021 May 7.

College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong Province, China; Qingdao National Laboratory for Marine Science and Technology, 266235, Qingdao, Shandong Province, China. Electronic address:

Emerging evidence suggests that the reduction of ethanolamine plasmalogen (PlsEtn) is associated with in Alzheimer's disease and metabolic diseases. However, the mechanistic bases for PlsEtn on the these diseases are not well understood. Plasmalogens are primarily synthesized in the liver and enriched in brain. Read More

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Lentivirus-Carried microRNA-195 Rescues Memory Deficits of Alzheimer's Disease Transgenic Mouse by Attenuating the Generation of Amyloid Plaques.

Front Pharmacol 2021 26;12:633805. Epub 2021 Apr 26.

Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, China.

Although lots of new drugs are developed to treat Alzheimer's disease (AD), many clinical trials of monotherapy have failed to affect disease progression or symptoms compared with placebo. Recently, scientists believe that combination treatment is more promising than monotherapy. Previous studies found that microRNA-195 () was down-regulated in the hippocampi and cortices of chronic brain hypoperfusion (CBH) rats and ApoE4 mice, and up-regulation of can improve the declined cognitive function of ApoE4 mice and CBH rats by targeting multi-genes that are related to AD pathology, including amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 (BACE1) genes. Read More

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