Last update 01 Nov 2024

Coagulation factor x APP

Last update 01 Nov 2024

Basic Info

Related Targets

Coagulation factorAPP

Drugs associated with Coagulation factor x APP

RU-505

Target

APP x Coagulation factor

Mechanism

APP inhibitors [+1]

Active Org.

The Rockefeller University

Originator Org.

The Rockefeller University

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Coagulation factor x APP

100 Translational Medicine associated with Coagulation factor x APP

0 Patents (Medical) associated with Coagulation factor x APP

105

Literatures (Medical) associated with Coagulation factor x APP

01 Nov 2024·Cell Reports

Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models

Article

Author: Cai, Catherine ; Honma, Patrick S ; Shin, Jia ; Yan, Zhaoqi ; Shen, Kevin ; Roberson, Erik D ; Ly, Katie K ; Saito, Takashi ; Ly, Katie K. ; Bauer, Pavol ; Miller, Stephanie R. ; Nambiar, Pranav ; Thomas, Reuben ; Pico, Alexander R ; Qiu, Yuechen ; Honma, Patrick S. ; Mendiola, Andrew S. ; Palop, Jorge J ; Lauderdale, Kelli ; Kaliss, Nick ; Miller, Stephanie R ; Mendiola, Andrew S ; Palop, Jorge J. ; Akassoglou, Katerina ; Remy, Stefan ; Luxem, Kevin ; Roberson, Erik D. ; Bullock, Mary ; Saido, Takaomi C. ; Mallen, K. Dakota ; Pico, Alexander R. ; Bangera, Shreya ; Saido, Takaomi C ; Mallen, K Dakota

Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in App^NL-G-F and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness. Notably, blocking fibrinogen-microglia interactions in 5xFAD-Fgg^γ390-396A mice largely prevented spontaneous behavioral alterations, indicating a key role for neuroinflammation. Thus, AD-related spontaneous behavioral alterations are prominent in knockin and transgenic models and sensitive to therapeutic interventions. VAME outcomes had higher specificity and sensitivity than conventional behavioral outcomes. We conclude that spontaneous behavior effectively captures age- and sex-dependent disease manifestations and treatment efficacy in AD models.

01 Jun 2024·Neuropsychopharmacology Reports

Search for cerebrospinal fluid biomarkers in patients with major psychiatric disorders: Multiplex immunoassay findings and proximity extension assay prospects

Review

Author: Hidese, Shinsuke

AbstractMultiplex immunoassays have been developed to detect multiple proteins simultaneously and are used to search for biomarkers, including those present in major psychiatric disorders. This study aimed to review multiplex immunoassay studies on cerebrospinal fluid (CSF) biomarkers in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) and examine future research directions using improved proteomic techniques. According to the results of previous multiplex immunoassay studies, increased CSF IFN‐β, IL‐8, MCP‐2, MMP‐2, PAI‐1, sICAM‐1, and sVCAM‐1 and decreased CSF ACE, APP, fibrinogen, and GDNF were observed in patients with schizophrenia, while CSF HGF and S100B were positively correlated with psychotic symptom and CSF IL‐11, IL‐29/IFN‐λ1, and TSLP were negatively correlated. Increased CSF IFN‐β and IL‐1β and decreased CSF Aβ42, APP, IL‐6, and NCAM‐1 were observed, while CSF S100B was positively correlated with manic symptom in patients with BD. Increased CSF IL‐4, MCP‐1, MIP‐1β, and MMP‐2 were observed in patients with MDD, while CSF HGF and MMP‐2 were positively correlated with depressive symptom and CSF IL‐15 and MCP‐1 were negatively correlated. However, signal cross‐talk and cross‐reactivity problems have been observed in previous studies using multiplex immunoassay. The proximity extension assay can be used to overcome cross‐reactivity and enable ultrasensitive multiplexed detection and quantification of more than 1000 target proteins. However, proteomic studies using proximity extension assay technology in patients with schizophrenia, BD, or MDD are still scarce. Therefore, future high‐quality proteomic studies are required to identify CSF biomarkers for larger sets of target proteins in patients with major psychiatric disorders.

23 Apr 2024·Proceedings of the National Academy of Sciences

Lecanemab blocks the effects of the Aβ/fibrinogen complex on blood clots and synapse toxicity in organotypic culture

Article

Author: Sharma, Anurag ; Simões-Pires, Elisa Nicoloso ; Torrente, Daniel ; Strickland, Sidney ; Norris, Erin H ; Chen, Zu-Lin ; Singh, Pradeep Kumar ; Calvano, Marissa

Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer’s disease (AD). Vascular deficits include a compromised blood–brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen’s interaction with the amyloid-beta (Aβ) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aβ plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen’s binding to Aβ protofibrils, preventing Aβ/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aβ/fibrinogen complex and prevents fibrinogen from exacerbating Aβ-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.

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