APP Human

Amyloid beta (A4) Precursor Protein Human Recombinant
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Description

Definition and Overview of APP Human

Amyloid-beta precursor protein (APP) is a single-pass transmembrane protein encoded by the APP gene on human chromosome 21. It is highly conserved across species and expressed in multiple tissues, with particularly high concentrations in neuronal synapses . APP undergoes proteolytic processing to generate fragments, including amyloid-beta (Aβ), which aggregates into plaques in Alzheimer’s disease .

APP Isoforms and Expression Patterns

Alternative splicing generates three major isoforms:

IsoformLength (aa)Expression ProfileKey Features
APP695695NeuronsLacks exon 7 and 8; predominant in CNS
APP751751Non-neuronal tissuesContains Kunitz protease inhibitor (KPI) domain
APP770770UbiquitousIncludes KPI and OX-2 domains

APP695 is critical for synaptic plasticity, while APP751/770 are linked to inflammation and cell adhesion .

Physiological Roles

  • Synaptic plasticity: Regulates synapse formation, repair, and long-term potentiation .

  • Iron homeostasis: Facilitates neuronal iron export via ferroportin interaction .

  • Antimicrobial activity: Secreted APP fragments (sAPPα) exhibit bactericidal properties .

Pathophysiological Roles

  • Alzheimer’s disease: Aβ accumulation from amyloidogenic APP processing drives plaque formation .

  • Neurodevelopmental disorders: Dysregulated APP splicing is implicated in autism and fragile X syndrome .

Genetic and Epigenetic Regulation

  • Mutations: Over 50 APP mutations are linked to familial AD (e.g., Swedish mutation K670N/M671L enhances Aβ production) .

  • Protective variant: A673T reduces Aβ generation by 40%, lowering AD risk .

  • Epigenetic control: Alternative splicing and genomic rearrangements influence APP expression in diseases like Lesch-Nyhan syndrome .

APP Processing Pathways

APP undergoes competing proteolytic pathways:

PathwayEnzymes InvolvedProductsBiological Outcome
Non-amyloidogenicα-secretase + γ-secretasesAPPα, P3, AICDNeuroprotective
Amyloidogenicβ-secretase + γ-secretasesAPPβ, Aβ, AICDNeurotoxic (Aβ plaques)

Key Insight: Shifting processing toward non-amyloidogenic cleavage is a therapeutic target .

Biomarker Potential

  • Plasma detection: APP gencDNA transcripts in blood plasma correlate with AD progression, offering non-invasive diagnostic potential .

  • Pangenome studies: The Human Pangenome Reference Consortium aims to resolve APP-linked genomic diversity, improving AD risk prediction .

Therapeutic Strategies

  • BACE1 inhibitors: Reduce Aβ production but face challenges in clinical trials .

  • Antisense oligonucleotides: Correct aberrant APP splicing in neurodevelopmental disorders .

Product Specs

Introduction
Amyloid beta A4 protein (APP) is a multifunctional protein that acts as a cell surface receptor and a transmembrane precursor. It undergoes cleavage by secretases, resulting in various peptides. Some of these peptides are secreted and can interact with the acetyltransferase complex APBB1/TIP60 to enhance transcriptional activation. In contrast, other peptides aggregate to form amyloid plaques, a hallmark of Alzheimer's disease, in the brain. Mutations in the APP gene are linked to autosomal dominant Alzheimer's disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy).
Description
Recombinant Human APP, expressed in E. coli, is a single, non-glycosylated polypeptide chain comprising 308 amino acids (18-289 a.a). It has a molecular mass of 34.7 kDa. Note: The molecular size observed on SDS-PAGE will be higher due to the presence of a 36 amino acid His-tag at the N-terminus. The protein is purified using proprietary chromatographic techniques.
Physical Appearance
Sterile Filtered colorless solution.
Formulation
The APP protein solution (0.5 mg/ml) is supplied in a buffer containing 20 mM Tris-HCl (pH 8.0), 20% glycerol, 0.1 M NaCl, and 1 mM DTT.
Stability
For short-term storage (up to 2-4 weeks), store the product at 4°C. For extended storage, freeze at -20°C. Adding a carrier protein (0.1% HSA or BSA) is advisable for long-term storage. Minimize repeated freeze-thaw cycles.
Purity
The purity is determined to be greater than 85.0% by SDS-PAGE analysis.
Synonyms
Amyloid beta A4 protein, ABPP, APPI, APP, Alzheimer disease amyloid protein, Cerebral vascular amyloid peptide, CVAP, PreA4, Protease nexin-II, PN-II, APP, A4, AD1, AAA, PN2, ABETA, CTFgamma.
Source
Escherichia Coli.
Amino Acid Sequence
MRGSHHHHHH GMASMTGGQQ MGRDLYDDDD KDRWGSLEVP TDGNAGLLAE PQIAMFCGRL NMHMNVQNGK WDSDPSGTKT CIDTKEGILQ YCQEVYPELQ ITNVVEANQP VTIQNWCKRG RKQCKTHPHF VIPYRCLVGE FVSDALLVPD KCKFLHQERM DVCETHLHWH TVAKETCSEK STNLHDYGML LPCGIDKFRG VEFVCCPLAE ESDNVDSADA EEDDSDVWWG GADTDYADGS EDKVVEVAEE EEVAEVEEEE ADDDEDDEDG DEVEEEAEEP YEEATERTTS IATTTTTTTE SVEEVVRE.

Q&A

What constitutes effective experimental design in human research applications?

Designing an effective experiment for human research involves several systematic steps to ensure valid results. The process begins with clearly defining research questions and formulating testable hypotheses. Researchers must identify both independent variables (what the experimenter changes) and dependent variables (what changes as a result of the manipulation)3 . For example, when studying how different learning methods affect knowledge retention, the learning method would be the independent variable and retention scores would be the dependent variable.

Controlling extraneous variables is crucial for maintaining internal validity. This requires identifying potential confounding factors such as participant demographics, environmental conditions, or prior knowledge that might influence outcomes. Systematic variable manipulation involves planning how to vary the independent variables while maintaining scientific rigor . For complex multi-attribute experiments, researchers must carefully control correlations among all independent variable factors to avoid confounding effects.

The experimental design must also include appropriate control conditions or groups to establish a baseline for comparison. This methodological approach ensures that observed effects can be attributed to the manipulated variables rather than to chance or uncontrolled factors.

How should researchers evaluate AI tools for human research applications?

When evaluating AI tools for human research applications, researchers should consider multiple factors beyond basic functionality. First, assess the tool's specific capabilities relative to your research needs. For literature reviews, tools like Litmaps offer powerful citation network visualization, while Semantic Scholar provides intelligent filtering and natural language processing to analyze millions of papers . Google Scholar offers broad academic search capabilities but lacks advanced visualization features and makes filtering quality papers challenging.

Second, evaluate data handling capabilities, including security measures, data integration options, and compatibility with existing research systems. Tools should seamlessly integrate with your current research workflow while protecting sensitive human subject data.

Third, consider verification mechanisms. AI-generated outputs should be verifiable through transparent algorithms and documentation. The duty of verification requires researchers to confirm the accuracy and reliability of AI-generated content before incorporating it into research findings .

Finally, assess the tool's learning curve relative to your team's technical expertise. Even powerful AI tools provide limited value if researchers cannot effectively implement them in their workflow. Select tools that balance sophisticated capabilities with usability appropriate for your research team.

What ethical frameworks should guide the use of applications in human research?

Ethical frameworks for applications in human research should address responsibilities across all research stages. Cornell University's framework identifies three fundamental duties: discretion, verification, and disclosure . The duty of discretion involves making informed choices about when and how to use research applications. The duty of verification requires confirming the accuracy and reliability of application-generated outputs. The duty of disclosure mandates transparently documenting how applications were used throughout the research process.

These duties apply across four key research stages: conception and execution, dissemination, translation, and funding compliance. During research conception and execution, researchers must maintain intellectual ownership while documenting application contributions. In the dissemination stage, researchers must follow journal and institution policies regarding disclosure of application use in publications. The translation stage requires verification of application-assisted translations for accuracy and cultural appropriateness. Finally, researchers must adhere to funder requirements regarding application use in the funding and compliance stage .

This ethical framework emphasizes that applications should be considered research tools that enhance scholarly advantage when used appropriately, with researchers maintaining responsibility for understanding how to use these tools wisely and ethically.

How can researchers effectively design multi-attribute experiments involving human subjects?

Designing multi-attribute experiments involving human subjects requires methodological rigor to produce valid and interpretable results. First, researchers must systematically manipulate independent variables by planning how each variable will be varied in a controlled manner . For example, in a diet study examining multiple nutritional factors, different groups might follow different meal plans with carefully controlled variations.

Second, researchers must determine the optimal scope and granularity of treatments. This involves deciding on the levels of treatment (e.g., low, medium, and high intensity of an exercise regimen) that will provide meaningful data without unnecessarily complicating the experiment . The granularity should be sufficient to detect meaningful effects but not so fine that it introduces excessive complexity.

Third, in complex multi-attribute experiments like conjoint experiments, the experimental design must carefully control correlations among all independent variable factors to avoid confounding effects . This often requires factorial or fractional factorial designs that allow for the examination of interactions between variables while minimizing the required number of experimental conditions.

Finally, researchers must implement appropriate randomization procedures to control for order effects and participant characteristics, particularly important when working with human subjects who may be influenced by learning effects or fatigue during the experiment.

What methodological approaches are recommended for analyzing contradictory data in human research?

When facing contradictory data in human research, methodological integrity demands a systematic approach rather than selectively reporting favorable results. Begin with systematic data verification by reviewing raw data for collection or recording errors, verifying instrument calibration, and checking for outliers that might distort findings. This fundamental verification ensures that contradictions stem from actual phenomena rather than methodological errors.

Next, implement statistical analysis of discrepancies using appropriate tests to assess the significance of contradictions. Consider whether statistical power or sample size limitations might explain apparent contradictions. When possible, employ multiple analytical methods to test the robustness of findings under different statistical assumptions.

Contextual interpretation represents another crucial step. Examine study limitations that might explain contradictions, including demographic variables, environmental factors, or procedural variations between studies. Review theoretical frameworks that might account for seemingly conflicting results, which may reveal that contradictions actually reflect different facets of a complex phenomenon rather than errors.

Finally, prioritize transparent reporting by documenting all contradictions rather than selectively reporting favorable data. Discuss possible explanations for discrepancies and suggest further research directions to resolve these contradictions. This methodological approach maintains research integrity while advancing scientific understanding through thorough examination of complex or contradictory findings.

How should Human-AI Collaboration (HAIC) be evaluated in research settings?

Evaluating Human-AI Collaboration (HAIC) in research settings requires a sophisticated framework that accounts for the complex interaction of human and AI components. An effective evaluation approach distinguishes between different HAIC modes: AI-Centric (where AI systems lead with human oversight), Human-Centric (where humans lead with AI assistance), and Symbiotic (where humans and AI systems work in equal partnership) .

The evaluation framework should include a structured decision tree to select relevant metrics based on the specific HAIC mode being employed. These metrics should incorporate both quantitative measures (such as efficiency gains, error rates, or time savings) and qualitative assessments (such as user satisfaction, perceived cognitive load, or quality of collaboration) .

The framework must also consider domain-specific requirements, as HAIC applications in medical research, social science, and other fields present unique challenges. The evaluation should assess both immediate performance outcomes and long-term impacts on research quality and researcher capabilities .

This systematic evaluation approach enables researchers to understand the effectiveness of human-AI collaboration in their specific research context, facilitating continuous improvement in how these collaborative systems are designed and implemented. The framework's practicality can be examined through application across diverse research domains, including healthcare, social sciences, and education .

What frameworks exist for integrating AI tools in different stages of human research?

A comprehensive framework for integrating AI tools across the human research lifecycle encompasses four distinct stages, each with specific applications and researcher responsibilities. The following table summarizes this framework based on research from Cornell University:

Research StageAI ApplicationsResearcher Responsibilities
Conception & ExecutionHypothesis generation, Literature review, Experimental designExercise discretion in selecting appropriate AI tools, Verify AI outputs, Document AI use
DisseminationManuscript drafting, Data visualization, TranslationAdhere to publication guidelines, Attribute AI contributions, Maintain scientific integrity
TranslationKnowledge transfer, Public communication, Educational materialsVerify accuracy, Ensure cultural appropriateness, Maintain message integrity
Funding & ComplianceGrant writing assistance, Budget planning, Compliance checksFollow funder requirements, Report methods transparently, Comply with institutional policies

This framework emphasizes that AI tools should be viewed as useful research tools that can enhance scholarly advantage when used appropriately. The research leader (principal investigator or lead author) bears responsibility for communicating expectations regarding AI use to research colleagues and students, and ultimately bears the consequences of intentional or incidental errors in tool use .

By addressing each research stage systematically, this framework provides a comprehensive approach to integrating AI tools while maintaining research integrity and transparency.

How can mobile applications enhance DNA sequencing analysis in human genetic research?

Mobile applications have transformed DNA sequencing analysis by making sophisticated genetic research tools accessible beyond traditional laboratory settings. Applications like DNAApp enable on-the-go decoding and visualization of ab1 DNA sequencing files on smartphones and tablets, addressing a significant limitation of browser-accessed web tools that cannot easily decode sequencing files .

These applications provide built-in analysis tools that facilitate rapid genetic data interpretation, including:

  • Reverse complementation to examine the complementary strand sequence

  • Protein translation to convert nucleotide sequences to amino acid sequences

  • Sequence-specific searching to identify target genetic elements

Furthermore, mobile applications can integrate with online bioinformatics platforms, creating a seamless workflow between field data collection and comprehensive analysis. This integration is particularly valuable for researchers conducting field work in remote locations or clinicians requiring rapid genetic analysis at point-of-care settings .

The high adoption rate of mobile devices among researchers makes these applications particularly valuable for enhancing productivity in biomedical research. As sequencing technologies continue to advance and generate larger datasets, mobile applications that can efficiently process and visualize this data will become increasingly important in human genetic research .

What criteria should researchers use to select appropriate AI research tools for human studies?

Researchers should apply a multi-dimensional evaluation framework when selecting AI research tools for human studies. First, assess the tool's specific capabilities relative to your research needs. Different tools offer varying strengths—for example, Google Scholar provides broad academic search capabilities but lacks advanced visualization features, while specialized tools like Litmaps offer powerful citation network visualization .

ToolFeaturesLimitations
Google ScholarBroad academic searchNo advanced visualization, difficulty filtering quality papers
ScopusAcademic database with citation analysisExpensive, not all journals included
Specialized AI ToolsTargeted analysis, visualization capabilitiesMay have narrower scope, steeper learning curve

Second, evaluate data handling capabilities, including security measures particularly critical for sensitive human subject data. Consider whether the tool complies with relevant data protection regulations and institutional requirements for human research data.

Third, assess verification mechanisms—AI-generated outputs should be verifiable through transparent algorithms and documentation. The verification process is especially important in human studies where research outcomes may influence clinical practice or policy decisions .

Fourth, consider integration with your existing research ecosystem. Tools should complement your current workflow rather than requiring substantial procedural changes. Finally, evaluate the cost-benefit ratio, considering both financial costs and time investments required to implement and master the tool relative to expected research benefits.

How should researchers navigate generative AI use across different stages of human research?

In the research dissemination stage, researchers must follow evolving journal and conference policies regarding AI disclosure. Many publications now require explicit attribution of AI contributions, and researchers must ensure human authors take full responsibility for the integrity of the work. Clear documentation of how generative AI was used in manuscript preparation is increasingly expected by academic publishers .

The research translation stage presents opportunities for using generative AI to make research findings accessible to different audiences. Researchers must verify AI-generated translations for accuracy and cultural appropriateness while maintaining human oversight of translation validity. This is particularly important when research findings may influence clinical practice or public health policy .

Finally, during the research funding and compliance stage, researchers must adhere to funder requirements regarding AI use, which are evolving rapidly. Transparent reporting of AI methods in grant applications is essential, as is ensuring compliance with institutional policies on AI in research. These considerations require researchers to remain current with rapidly evolving guidelines while maintaining research integrity throughout the process .

What are the most effective approaches for controlling extraneous variables in human research applications?

Controlling extraneous variables in human research requires methodological rigor to isolate the effects of independent variables. Randomization represents one of the most powerful approaches, randomly assigning participants to conditions to distribute unknown or unmeasured extraneous variables evenly across groups. This technique helps ensure that systematic differences between groups are minimized, strengthening internal validity .

Matching participants on relevant characteristics provides another effective approach, particularly when complete randomization is not feasible. By ensuring that participants in different conditions have similar characteristics (e.g., age, education level, prior experience), researchers can reduce the influence of these potential confounding variables on the dependent measure .

Statistical control methods offer a post-hoc approach to account for extraneous variables. Techniques such as analysis of covariance (ANCOVA) or multiple regression allow researchers to statistically adjust for the influence of measured variables that could not be controlled experimentally. This approach is particularly valuable in field studies where experimental control is limited.

Finally, standardization of procedures ensures that all participants experience consistent experimental conditions. This includes standardizing instructions, testing environments, measurement procedures, and timing. Standardization reduces the impact of procedural variations that might introduce error variance into the dependent measure .

These approaches can be combined to create a robust methodology that maximizes internal validity while maintaining external validity in human research applications.

How can researchers effectively distinguish between correlation and causation in human studies using application data?

Distinguishing between correlation and causation remains one of the most challenging aspects of human research, particularly when analyzing application-generated data. Experimental design provides the most robust approach for establishing causation. True experiments with random assignment, control groups, and systematic manipulation of independent variables allow researchers to conclude that observed effects are likely causal rather than merely correlational .

Temporal precedence offers another important consideration—for causation to exist, the cause must precede the effect. Longitudinal research designs that collect data at multiple time points can help establish this temporal ordering, strengthening causal inferences beyond what cross-sectional designs permit.

What emerging trends are shaping the application of AI in human research?

Several significant trends are transforming AI applications in human research. First, we're witnessing the integration of AI across the entire research lifecycle—from conception through dissemination and translation. This holistic integration is creating new opportunities for efficiency while raising important methodological questions about how AI contributions should be documented and evaluated .

Second, the development of specialized mobile applications for field research and data collection is expanding research capabilities beyond traditional laboratory settings. Applications like DNAApp demonstrate how mobile tools can facilitate sophisticated analyses that previously required specialized equipment and facilities . This democratization of research tools enables more diverse research approaches and settings.

Third, there's growing emphasis on ethical frameworks specifically designed for AI use in human studies. Cornell University's framework identifying the duties of discretion, verification, and disclosure exemplifies how research communities are developing normative guidelines to ensure responsible AI use . These frameworks acknowledge both the potential benefits and risks of AI tools in research contexts.

Fourth, evaluation methodologies for human-AI collaboration are evolving to address the unique dynamics of these partnerships. Frameworks distinguishing between AI-Centric, Human-Centric, and Symbiotic collaboration modes provide more nuanced approaches to assessing effectiveness beyond simple performance metrics .

Finally, there's increasing focus on transparency and disclosure of AI contributions throughout the research process. As AI tools become more sophisticated, clearly documenting their role becomes essential for research integrity and reproducibility. These trends collectively suggest that future applications in human research will continue to enhance capabilities while requiring thoughtful navigation of methodological and ethical considerations.

Product Science Overview

Introduction

Amyloid beta (A4) precursor protein (APP) is a transmembrane protein that plays a crucial role in the development and function of the nervous system. It is widely expressed in various tissues, with higher concentrations found in the brain . The human recombinant form of this protein is used extensively in research to understand its structure, function, and role in diseases, particularly Alzheimer’s disease.

Structure and Function

APP is a cell surface receptor that performs several physiological functions on the surface of neurons. These functions include neurite growth, neuronal adhesion, and axonogenesis . The protein undergoes sequential proteolytic processing by enzymes known as secretases, leading to the generation of amyloid-beta (Aβ) peptides of different lengths .

Proteolytic Processing

The proteolytic processing of APP involves two main pathways: the non-amyloidogenic pathway and the amyloidogenic pathway. In the non-amyloidogenic pathway, APP is cleaved by α-secretase, resulting in the release of a soluble APP fragment (sAPPα) and a membrane-bound C-terminal fragment (CTFα). This pathway precludes the formation of Aβ peptides.

In the amyloidogenic pathway, APP is first cleaved by β-secretase, producing a soluble APP fragment (sAPPβ) and a membrane-bound C-terminal fragment (CTFβ). The CTFβ is then further cleaved by γ-secretase, resulting in the release of Aβ peptides . These Aβ peptides can aggregate to form amyloid plaques, which are a hallmark of Alzheimer’s disease .

Role in Alzheimer’s Disease

Aβ peptides are the major component of amyloid plaques found in the brains of Alzheimer’s patients . The aggregation of these peptides is believed to play a central role in the pathogenesis of Alzheimer’s disease. Mutations in the APP gene have been implicated in autosomal dominant Alzheimer’s disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy) .

Research and Applications

Human recombinant APP is used in various research applications to study its structure, function, and role in disease. It is also used to develop therapeutic strategies aimed at modulating APP processing and reducing Aβ peptide formation. Understanding the mechanisms underlying APP processing and Aβ aggregation is crucial for developing effective treatments for Alzheimer’s disease.

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