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A Step-To-Step Guide to Write a Quality Research Article

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• First Online: 01 June 2023
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• Amit Kumar Tyagi   ORCID: orcid.org/0000-0003-2657-8700 14 ,
• Rohit Bansal 15 ,
• Anshu 16 &
• Sathian Dananjayan   ORCID: orcid.org/0000-0002-6103-7267 17  

Part of the book series: Lecture Notes in Networks and Systems ((LNNS,volume 717))

Included in the following conference series:

• International Conference on Intelligent Systems Design and Applications

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Today publishing articles is a trend around the world almost in each university. Millions of research articles are published in thousands of journals annually throughout many streams/sectors such as medical, engineering, science, etc. But few researchers follow the proper and fundamental criteria to write a quality research article. Many published articles over the web become just irrelevant information with duplicate information, which is a waste of available resources. This is because many authors/researchers do not know/do not follow the correct approach for writing a valid/influential paper. So, keeping such issues for new researchers or exiting researchers in many sectors, we feel motivated to write an article and present some systematic work/approach that can help researchers produce a quality research article. Also, the authors can publish their work in international conferences like CVPR, ICML, NeurIPS, etc., or international journals with high factors or a white paper. Publishing good articles improve the profile of researchers around the world, and further future researchers can refer their work in their work as references to proceed with the respective research to a certain level. Hence, this article will provide sufficient information for researchers to write a simple, effective/impressive and qualitative research article on their area of interest.

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Nair, M.M., Tyagi, A.K., Sreenath, N.: The future with industry 4.0 at the core of society 5.0: open issues, future opportunities and challenges. In: 2021 International Conference on Computer Communication and Informatics (ICCCI), pp. 1–7 (2021). https://doi.org/10.1109/ICCCI50826.2021.9402498

Tyagi, A.K., Fernandez, T.F., Mishra, S., Kumari, S.: Intelligent Automation Systems at the Core of Industry 4.0. In: Abraham, A., Piuri, V., Gandhi, N., Siarry, P., Kaklauskas, A., Madureira, A. (eds.) ISDA 2020. AISC, vol. 1351, pp. 1–18. Springer, Cham (2021). https://doi.org/10.1007/978-3-030-71187-0_1

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Varsha, R., Nair, S.M., Tyagi, A.K., Aswathy, S.U., RadhaKrishnan, R.: The future with advanced analytics: a sequential analysis of the disruptive technology’s scope. In: Abraham, A., Hanne, T., Castillo, O., Gandhi, N., Nogueira Rios, T., Hong, T.-P. (eds.) HIS 2020. AISC, vol. 1375, pp. 565–579. Springer, Cham (2021). https://doi.org/10.1007/978-3-030-73050-5_56

Tyagi, A.K., Nair, M.M., Niladhuri, S., Abraham, A.: Security, privacy research issues in various computing platforms: a survey and the road ahead. J. Inf. Assur. Secur. 15 (1), 1–16 (2020)

Madhav, A.V.S., Tyagi, A.K.: The world with future technologies (Post-COVID-19): open issues, challenges, and the road ahead. In: Tyagi, A.K., Abraham, A., Kaklauskas, A. (eds.) Intelligent Interactive Multimedia Systems for e-Healthcare Applications, pp. 411–452. Springer, Singapore (2022). https://doi.org/10.1007/978-981-16-6542-4_22

Mishra, S., Tyagi, A.K.: The role of machine learning techniques in the Internet of Things-based cloud applications. In: Pal, S., De, D., Buyya, R. (eds.) Artificial Intelligence-Based Internet of Things Systems. Internet of Things (Technology, Communications and Computing). Springer, Cham. https://doi.org/10.1007/978-3-030-87059-1_4

Pramod, A., Naicker, H.S., Tyagi, A.K.: Machine Learning and Deep Learning: Open Issues and Future Research Directions for Next Ten Years. Computational Analysis and Understanding of Deep Learning for Medical Care: Principles, Methods, and Applications. Wiley Scrivener (2020)

Kumari, S., Tyagi, A.K., Aswathy, S.U.: The Future of Edge Computing with Blockchain Technology: Possibility of Threats, Opportunities and Challenges. In the Book Recent Trends in Blockchain for Information Systems Security and Privacy. CRC Press, Boca Raton (2021)

Dananjayan, S., Tang, Y., Zhuang, J., Hou, C., Luo, S.: Assessment of state-of-the-art deep learning based citrus disease detection techniques using annotated optical leaf images. Comput. Electron. Agric. 193 (7), 106658 (2022). https://doi.org/10.1016/j.compag.2021.106658

Nair, M.M., Tyagi, A.K.: Privacy: History, Statistics, Policy, Laws, Preservation and Threat analysis. J. Inf. Assur. Secur. 16 (1), 24–34 (2021)

Tyagi, A.K., Sreenath, N.: A comparative study on privacy preserving techniques for location based services. Br. J. Math. Comput. Sci. 10 (4), 1–25 (2015). ISSN: 2231–0851

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Ambildhuke, G.M., Rekha, G., Tyagi, A.K.: Performance analysis of undersampling approaches for solving customer churn prediction. In: Goyal, D., Gupta, A.K., Piuri, V., Ganzha, M., Paprzycki, M. (eds.) Proceedings of the Second International Conference on Information Management and Machine Intelligence. LNNS, vol. 166, pp. 341–347. Springer, Singapore (2021). https://doi.org/10.1007/978-981-15-9689-6_37

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Department of Fashion Technology, National Institute of Fashion Technology, New Delhi, India

Amit Kumar Tyagi

Department of Management Studies, Vaish College of Engineering, Rohtak, India

Rohit Bansal

Faculty of Management and Commerce (FOMC), Baba Mastnath University, Asthal Bohar, Rohtak, India

School of Computer Science and Engineering, Vellore Institute of Technology, Chennai, Tamilnadu, 600127, India

Sathian Dananjayan

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Amit Kumar Tyagi & Sathian Dananjayan have drafted and approved this manuscript for final publication.

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Faculty of Computing and Data Science, FLAME University, Pune, Maharashtra, India

Ajith Abraham

Center for Smart Computing Continuum, Burgenland, Austria

Sabri Pllana

University of Bari, Bari, Italy

Gabriella Casalino

University of Jinan, Jinan, Shandong, China

Department of Computer Science and Engineering, Thapar Institute of Engineering and Technology, Patiala, Punjab, India

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As the author belongs to the computer science stream, so he has tried to cover up this article for all streams, but the maximum example used in situations, languages, datasets etc., are with respect to computer science-related disciplines only. This work can be used as a reference for writing good quality papers for international conferences journals.

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Tyagi, A.K., Bansal, R., Anshu, Dananjayan, S. (2023). A Step-To-Step Guide to Write a Quality Research Article. In: Abraham, A., Pllana, S., Casalino, G., Ma, K., Bajaj, A. (eds) Intelligent Systems Design and Applications. ISDA 2022. Lecture Notes in Networks and Systems, vol 717. Springer, Cham. https://doi.org/10.1007/978-3-031-35510-3_36

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How to write a research article to submit for publication

Pharmacists and healthcare professionals who are undertaking research should have an understanding of how to produce a research article for publication, and be aware of the important considerations relating to submission to a peer-reviewed journal.

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Undertaking and performing scientific, clinical and practice-based research is only the beginning of the scholarship of discovery [1] . For the full impact of any research to be achieved and to have an effect on the wider research and scientific community, it must be published in an outlet accessible to relevant professionals [2] .

Scientific research is often published in peer-reviewed journals. Peer review is defined as the unbiased, independent, critical assessment of scholarly or research manuscripts submitted to journals by experts or opinion leaders [3] . The process and requirements of reviewers has been covered recently [4] . On account of this rigorous process, peer-reviewed scientific journals are considered the primary source of new information that impacts and advances clinical decision-making and practice [5] , [6] .

The development of a research article can be helpful for the promotion of scientific thinking [7] , [8] and the advancement of effective writing skills, allowing the authors to participate in broader scientific discussions that lie beyond their scope of practice or discipline [2] .

This article aims to provide pharmacists and healthcare professionals who are undertaking research with an understanding of how to produce a research article for publication, as well as points to consider before submission to a peer-reviewed journal.

Importance of the research question

This article will not go into detail about forming suitable research questions, however, in principle, a good research question will be specific, novel and of relevance to the scientific community (e.g. pharmacy – pharmacists, pharmaceutical scientists, pharmacy technicians and related healthcare professionals). Hulley et al . suggest using the FINER criteria (see ‘Figure 1: FINER criteria for a good research question’) to aid the development of a good research question [9] .

Figure 1: FINER criteria for a good research question

Source: Hulley S, Cummings S, Browner W  et al . [9]

The FINER criteria highlight useful points that may generally increase the chances of developing a successful research project. A good research question should specify the population of interest, be of interest to the scientific community and potentially to the public, have clinical relevance and further current knowledge in the field.

Having a clear research question that is of interest to those working in the same field will help in the preparation of an article because it can be used as the central organising principle – all of the content included and discussed should focus on answering this question.

Preparing a first draft

Before writing the article, it is useful to highlight several journals that you could submit the final article to. It also helps to familiarise yourself with these journals’ styles, article structures and formatting instructions before starting to write. Many journals also have criteria that research articles should be able to satisfy. For example, all research article submissions to  Clinical Pharmacist must demonstrate innovative or novel results that are sustainable, reproducible and transferable [10] .

Having researched potential target journals, you should have a clear idea about your target audience, enabling you to pitch the level of the article appropriately [11] (see ‘Box 1: Top tips to prepare for writing’).

Box 1: Top tips to prepare for writing

• Know the focus of the paper – identify two or three important findings and make these the central theme of the article;
• Gather important data, perform any analyses and make rough data plots and tables beforehand. These can then be refined for inclusion or submitted as supplementary information if needed;
• Organise your results to flow in a logical sequence;
• Know the structure and requirements of your target journals (check websites and author guidelines, as well as published articles);
• Think about the style of the piece and look to pitch the article at the level of the intended audience;
• Clarity should be your guiding principle.

Structuring a research article

Most research articles follow a similar structure and format that includes an abstract, introduction, methods, results and discussion, as well as a summary of the key points discussed in the article.

One approach is to start with the methods section, which can be derived from the protocol and any pilot phase. Many of the figures and tables can be constructed in advance, which will help with writing the results section. The questions addressed by the study can be used alongside the results to formulate the introduction, which can guide how the discussion is written [11] .

Clinical Pharmacist , like other peer-reviewed journals, has specific author guidelines and formatting instructions to help authors prepare their articles [10] , [12] , [13] . The following sections will discuss the required sections and important considerations for authors when writing.

Title, abstract and keywords

The title, abstract and keywords are essential to the successful communication of research. Most electronic search engines, databases (e.g. PubMed/MEDLINE) and journal websites extract words from them to determine whether your article will be displayed to interested readers [14] , [15] , [16] , [17] , enabling accurate dissemination and leading to future citations.

In addition, the title and abstract are usually freely available online. If an article is not published in an ‘open access’ format, (i.e. it is free and immediately available online and access is combined with the rights to use these articles fully in the digital environment) [18] , or if the reader does not have a subscription to the journal, they will have to decide on whether to pay to access the full article to continue reading. Therefore, it is imperative that they are informative and accurate.

The title should accurately reflect the research, identify the main issue and begin with the subject matter, while being both simple and enticing enough to attract the audience [19] . Authors should avoid using ‘a study of’, ‘investigations into’ and ‘observations on’ in titles. It is also worth remembering that abstracting and indexing services, such as MEDLINE, require accurate titles, because they extract keywords from them for cross-referencing [19] .

Many journals require the abstract to be structured in the same way as the main headings of the paper (e.g. introduction, methods, results, discussion and conclusion) and to be around 150–300 words in length [10] . In general, references should not be cited in the abstract.

Introduction

The introduction should provide the background and context to the study. Two or three paragraphs can be dedicated to the discussion of any previous work and identification of gaps in current knowledge. The rest of the introduction should then outline what this piece of work aims to address and why this is important, before stating the objectives of the study and the research question [20] .

The methods section should provide the reader with enough detail for them to be able to reproduce the study if desired [3] . The context and setting of the study should be described and the study design specified. The section should further describe the population (including the inclusion and exclusion criteria), sampling strategy and the interventions performed. The main study variables should be identified and the data collection procedures described [3] .

Authors should provide specific, technical and detailed information in this section. Several checklists and guidelines are available for the reporting of specific types of studies:

• CONSORT is used for developing and reporting a randomised controlled trial [21] ;
• The STARD checklist can help with designing a diagnostic accuracy study [22] ;
• The PRISMA checklist can be used when performing a metaâ€analyses or systematic review, but can also help with compiling an introduction [23] .

For the reporting of qualitative research studies, authors should explain which research tradition the study utilises and link the choice of methodological strategies with the research goals [24] .

For studies describing the development of new initiatives or clinical services, authors should describe the situation before the initiative began, the establishment of priorities, formulation of objectives and strategies, mobilisation of resources, and processes used in the methods section [10] .

The final portion of the methods section will include the statistical methods used to analyse the data [25] . The statistical methods employed should be described with enough detail to enable a knowledgeable reader with access to the original data to be able to judge its appropriateness for the study and verify the results [3] . For survey-based studies and information on sampling frame, size and statistical powers, see ‘When to use a survey in pharmacy practice research’ [26] .

Findings should be quantified and presented with appropriate indicators of measurement error or uncertainty (e.g. confidence intervals). Authors should avoid relying solely on statistical hypothesis testing, such as P values, because these fail to convey important information about effect size and precision of estimates [3] . Statistical terms, abbreviations and most symbols should be defined, and the statistical software package and versions used should be specified. Authors should also take care to distinguish prespecified from exploratory analyses, including subgroup analyses [3] .

The results section should be straightforward and factual and all of the results that relate to the research question should be provided, with detail including simple counts and percentages [27] . Data collection and recruitment should be commented on and the participants described. Secondary findings and the results of subgroup analyses can also be presented [27] .

Figures, schemes and tables

To present data and results of the research study, figures, schemes and tables can be used. They should include significant digits, error bars and levels of statistical significance.

Tables should be presented with a summary title, followed by caption, a sentence or two that describes the content and impact of the data included in the table. All captions should provide enough detail so that the table or figure can be interpreted and understood as stand-alone material, separate from the article.

Figures should also be presented with a summary title, a caption that describes the significant result or interpretation that can be made from the figure, the number of repetitions within the experiment, as well as what the data point actually represents. All figures and tables should be cited in the manuscript text [11] .

When compiling tables and figures, important statistics, such as the number of samples (n), the index of dispersion (standard deviation [SD], standard error of the mean [SEM]), and the index of central tendency (mean, median or mode), must be stated. The statistical analysis performed should also be included and specific statistical data should be indicated (e.g. P values) [11] .

Discussion and conclusions

The discussion section should state the main findings of the study. The main results should be compared with reference to previous research and current knowledge, and where this has been extended it should be fully described [2] , [11] , [25] . For clinical studies, relevant discussion of the implications the results may have on policy should be included [10] . It is important to include an analysis of the strengths and limitations of the study and offer perspectives for future work [2] . Excessive presentation of data and results without any discussion should be avoided and it is not necessary to cite a published work for each argument presented. Any conclusions should include the major findings, followed by a brief discussion of future perspectives and the application of this work to other disciplines [10] .

The list of references should be appropriate; important statements presented as facts should be referenced, as well as the methods and instruments used. Reference lists for research articles, however, unlike comprehensive reviews of a topic, do not necessarily have to be exhaustive. References to unpublished work, to documents in the grey literature (technical reports), or to any source that the reader will have difficulty finding or understanding should be avoided [27] . Most journals have reference limits and specific formatting requirements, so it is important to check the journal’s author guidelines [10] , [11] , [12] , [13] , [19] .

Authorship and acknowledgements

Determining contributors who qualify as authors and those who should be acknowledged can be difficult. Clinical Pharmacist follows guidance from the International Committee of Medical Journal Editors, which recommends that authorship be based on the following four criteria:

• Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND
• Drafting the work or revising it critically for important intellectual content; AND
• Final approval of the version to be published; AND
• Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved [3] .

Therefore, only individuals who meet all four criteria should be identified as authors [3] . The contribution of individuals who do not meet all four criteria should instead be included in the acknowledgements.

In addition, a statement that recognises any funding sources for the work should be added to the acknowledgements. This statement should adhere to the guidelines provided by the funding institution [11] .

Supplementary and supporting information

A key principle of research publication is that others should be able to replicate and build upon an author’s published claims. Therefore, submitted manuscripts should contain the necessary detail about the study and analytical design, and the data must be available for editors and peer-reviewers to allow full evaluation to take place. This is now commonplace and is seen as best practice. Author guidelines now include sections related to misconduct and falsification of data [28] . By participating in self-archiving practices and providing full data sets, authors can play their part in transparency.

The Royal Pharmaceutical Society website hosts a database to help share data from research studies. The map of evidence collates existing evidence and ongoing initiatives that can ultimately inform policy and practice relating to pharmacy; enables the sharing and showcasing of good pharmacy practice and innovation; and aims to increase the knowledge exchange and learning in pharmacy and pharmaceutical sciences [29] .

Revising your article prior to submission

Once a draft research article has been prepared, it should be shared among all of the co-authors for review and comments. A full revision of the draft should then take place to correct grammar and check flow and logic before journal submission. All authors will have to agree on the authenticity of the data and presentation before formal submission can take place [3] (see ‘Box 2: Common mistakes and reasons why research articles are rejected for publication’).

Box 2: Common mistakes and reasons why research articles are rejected for publication

• Lack of novelty and importance of the research question;
• Poor study design;
• Methods not accurately and adequately described;
• Results poorly reported, along with little analysis of data;
• Lack of statistical analysis;
• Not acknowledging the study’s limitations;
• Providing unsupported conclusions or overstating the results of the study;
• Poor writing;
• Not following the journal’s style and formatting guidance;
• Submitting a manuscript that is incomplete or outside of the aims and scope.

Selecting a journal and submitting your manuscript

It is important to select a journal for submission wisely because this choice can determine the impact and dissemination of your work [13] . Impact factor (a measure of the frequency with which the average article in a journal has been cited in a particular year), the scope and readership of a title may also influence your choice.

Furthermore, approval and adequate disclosures must be obtained from all co-authors. A conflict of interests form is also completed as part of the submissions process (normally completed by the lead author on behalf of all authors).

Many journals now request that a cover letter is also submitted to the editor, putting the study in context and explaining why the research is of importance to their audience and why it should be considered for publication in their journal.

Once this is all completed, the article can be formally submitted (usually via email or an online submission system). Figure 2 provides a sample process for a manuscript once submitted to a journal for consideration for publication.

Figure 2: Sample process for a submitted manuscript

Source: The Pharmaceutical Journal

All journals follow a similar process for article submissions, whether they use a formal online submissions system or simply email.  Clinical Pharmacist uses a process similar to this and it is useful for authors to be aware of how their submission may progress once submitted to a journal for publication.

Useful Links

• The EQUATOR Network
• Research4Life – Authorship skills modules
• Pharmacy Research UK

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You can use the following forms to record your learning and action points from this article from Pharmaceutical Journal Publications.

Your CPD module results are stored against your account here at The Pharmaceutical Journal . You must be registered and logged into the site to do this. To review your module results, go to the ‘My Account’ tab and then ‘My CPD’.

Any training, learning or development activities that you undertake for CPD can also be recorded as evidence as part of your RPS Faculty practice-based portfolio when preparing for Faculty membership. To start your RPS Faculty journey today, access the portfolio and tools at www.rpharms.com/Faculty

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• Published: 06 May 2024

APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease

• Juan Fortea   ORCID: orcid.org/0000-0002-1340-638X 1 , 2 , 3   na1 ,
• Jordi Pegueroles   ORCID: orcid.org/0000-0002-3554-2446 1 , 2 ,
• Daniel Alcolea   ORCID: orcid.org/0000-0002-3819-3245 1 , 2 ,
• Olivia Belbin   ORCID: orcid.org/0000-0002-6109-6371 1 , 2 ,
• Oriol Dols-Icardo   ORCID: orcid.org/0000-0003-2656-8748 1 , 2 ,
• Lídia Vaqué-Alcázar 1 , 4 ,
• Laura Videla   ORCID: orcid.org/0000-0002-9748-8465 1 , 2 , 3 ,
• Juan Domingo Gispert 5 , 6 , 7 , 8 , 9 ,
• Marc Suárez-Calvet   ORCID: orcid.org/0000-0002-2993-569X 5 , 6 , 7 , 8 , 9 ,
• Sterling C. Johnson   ORCID: orcid.org/0000-0002-8501-545X 10 ,
• Reisa Sperling   ORCID: orcid.org/0000-0003-1535-6133 11 ,
• Alexandre Bejanin   ORCID: orcid.org/0000-0002-9958-0951 1 , 2 ,
• Alberto Lleó   ORCID: orcid.org/0000-0002-2568-5478 1 , 2 &
• Víctor Montal   ORCID: orcid.org/0000-0002-5714-9282 1 , 2 , 12   na1  

Nature Medicine ( 2024 ) Cite this article

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• Alzheimer's disease
• Predictive markers

This study aimed to evaluate the impact of APOE4 homozygosity on Alzheimer’s disease (AD) by examining its clinical, pathological and biomarker changes to see whether APOE4 homozygotes constitute a distinct, genetically determined form of AD. Data from the National Alzheimer’s Coordinating Center and five large cohorts with AD biomarkers were analyzed. The analysis included 3,297 individuals for the pathological study and 10,039 for the clinical study. Findings revealed that almost all APOE4 homozygotes exhibited AD pathology and had significantly higher levels of AD biomarkers from age 55 compared to APOE3 homozygotes. By age 65, nearly all had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, with the prevalence of these markers increasing with age, indicating near-full penetrance of AD biology in APOE4 homozygotes. The age of symptom onset was earlier in APOE4 homozygotes at 65.1, with a narrower 95% prediction interval than APOE3 homozygotes. The predictability of symptom onset and the sequence of biomarker changes in APOE4 homozygotes mirrored those in autosomal dominant AD and Down syndrome. However, in the dementia stage, there were no differences in amyloid or tau positron emission tomography across haplotypes, despite earlier clinical and biomarker changes. The study concludes that APOE4 homozygotes represent a genetic form of AD, suggesting the need for individualized prevention strategies, clinical trials and treatments.

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Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study

Association of APOE e2 genotype with Alzheimer’s and non-Alzheimer’s neurodegenerative pathologies

Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies

Data availability.

Access to tabular data from ADNI ( https://adni.loni.usc.edu/ ), OASIS ( https://oasis-brains.org/ ), A4 ( https://ida.loni.usc.edu/collaboration/access/appLicense.jsp ) and NACC ( https://naccdata.org/ ) can be requested online, as publicly available databases. All requests will be reviewed by each studyʼs scientific board. Concrete inquiries to access the WRAP ( https://wrap.wisc.edu/data-requests-2/ ) and ALFA + ( https://www.barcelonabeta.org/en/alfa-study/about-the-alfa-study ) cohort data can be directed to each study team for concept approval and feasibility consultation. Requests will be reviewed to verify whether the request is subject to any intellectual property.

Code availability

All statistical analyses and raw figures were generated using R (v.4.2.2). We used the open-sourced R packages of ggplot2 (v.3.4.3), dplyr (v.1.1.3), ggstream (v.0.1.0), ggpubr (v.0.6), ggstatsplot (v.0.12), Rmisc (v.1.5.1), survival (v.3.5), survminer (v.0.4.9), gtsummary (v.1.7), epitools (v.0.5) and statsExpression (v.1.5.1). Rscripts to replicate our findings can be found at https://gitlab.com/vmontalb/apoe4-asdad (ref. 32 ). For neuroimaging analyses, we used Free Surfer (v.6.0) and ANTs (v.2.4.0).

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Acknowledgements

We acknowledge the contributions of several consortia that provided data for this study. We extend our appreciation to the NACC, the Alzheimer’s Disease Neuroimaging Initiative, The A4 Study, the ALFA Study, the Wisconsin Register for Alzheimer’s Prevention and the OASIS3 Project. Without their dedication to advancing Alzheimer’s disease research and their commitment to data sharing, this study would not have been possible. We also thank all the participants and investigators involved in these consortia for their tireless efforts and invaluable contributions to the field. We also thank the institutions that funded this study, the Fondo de Investigaciones Sanitario, Carlos III Health Institute, the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas and the Generalitat de Catalunya and La Caixa Foundation, as well as the NIH, Horizon 2020 and the Alzheimer’s Association, which was crucial for this research. Funding: National Institute on Aging. This study was supported by the Fondo de Investigaciones Sanitario, Carlos III Health Institute (INT21/00073, PI20/01473 and PI23/01786 to J.F., CP20/00038, PI22/00307 to A.B., PI22/00456 to M.S.-C., PI18/00435 to D.A., PI20/01330 to A.L.) and the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas Program 1, partly jointly funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una Manera de Hacer Europa. This work was also supported by the National Institutes of Health grants (R01 AG056850; R21 AG056974, R01 AG061566, R01 AG081394 and R61AG066543 to J.F., S10 OD025245, P30 AG062715, U54 HD090256, UL1 TR002373, P01 AG036694 and P50 AG005134 to R.S.; R01 AG027161, R01 AG021155, R01 AG037639, R01 AG054059; P50 AG033514 and P30 AG062715 to S.J.) and ADNI (U01 AG024904), the Department de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca I Innovació en Salut (SLT006/17/00119 to J.F.; SLT002/16/00408 to A.L.) and the A4 Study (R01 AG063689, U24 AG057437 to R.A.S). It was also supported by Fundación Tatiana Pérez de Guzmán el Bueno (IIBSP-DOW-2020-151 o J.F.) and Horizon 2020–Research and Innovation Framework Programme from the European Union (H2020-SC1-BHC-2018-2020 to J.F.; 948677 and 847648 to M.S.-C.). La Caixa Foundation (LCF/PR/GN17/50300004 to M.S.-C.) and EIT Digital (Grant 2021 to J.D.G.) also supported this work. The Alzheimer Association also participated in the funding of this work (AARG-22-923680 to A.B.) and A4/LEARN Study AA15-338729 to R.A.S.). O.D.-I. receives funding from the Alzheimer’s Association (AARF-22-924456) and the Jerome Lejeune Foundation postdoctoral fellowship.

Author information

These authors contributed equally: Juan Fortea, Víctor Montal.

Authors and Affiliations

Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau, Barcelona, Spain

Juan Fortea, Jordi Pegueroles, Daniel Alcolea, Olivia Belbin, Oriol Dols-Icardo, Lídia Vaqué-Alcázar, Laura Videla, Alexandre Bejanin, Alberto Lleó & Víctor Montal

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas. CIBERNED, Barcelona, Spain

Juan Fortea, Jordi Pegueroles, Daniel Alcolea, Olivia Belbin, Oriol Dols-Icardo, Laura Videla, Alexandre Bejanin, Alberto Lleó & Víctor Montal

Barcelona Down Medical Center, Fundació Catalana Síndrome de Down, Barcelona, Spain

Juan Fortea & Laura Videla

Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain

Lídia Vaqué-Alcázar

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain

Juan Domingo Gispert & Marc Suárez-Calvet

Neurosciences Programme, IMIM - Hospital del Mar Medical Research Institute, Barcelona, Spain

Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain

Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina. Instituto de Salud carlos III, Madrid, Spain

Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA

Sterling C. Johnson

Brigham and Women’s Hospital Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Reisa Sperling

Barcelona Supercomputing Center, Barcelona, Spain

Víctor Montal

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Contributions

J.F. and V.M. conceptualized the research project and drafted the initial manuscript. V.M., J.P. and J.F. conducted data analysis, interpreted statistical findings and created visual representations of the data. O.B. and O.D.-I. provided valuable insights into the genetics of APOE. L.V., A.B. and L.V.-A. meticulously reviewed and edited the manuscript for clarity, accuracy and coherence. J.D.G., M.S.-C., S.J. and R.S. played pivotal roles in data acquisition and securing funding. A.L. and D.A. contributed to the study design, offering guidance and feedback on statistical analyses, and provided critical review of the paper. All authors carefully reviewed the manuscript, offering pertinent feedback that enhanced the study’s quality, and ultimately approved the final version.

Corresponding authors

Correspondence to Juan Fortea or Víctor Montal .

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Competing interests.

S.C.J. has served at scientific advisory boards for ALZPath, Enigma and Roche Diagnostics. M.S.-C. has given lectures in symposia sponsored by Almirall, Eli Lilly, Novo Nordisk, Roche Diagnostics and Roche Farma, received consultancy fees (paid to the institution) from Roche Diagnostics and served on advisory boards of Roche Diagnostics and Grifols. He was granted a project and is a site investigator of a clinical trial (funded to the institution) by Roche Diagnostics. In-kind support for research (to the institution) was received from ADx Neurosciences, Alamar Biosciences, Avid Radiopharmaceuticals, Eli Lilly, Fujirebio, Janssen Research & Development and Roche Diagnostics. J.D.G. has served as consultant for Roche Diagnostics, receives research funding from Hoffmann–La Roche, Roche Diagnostics and GE Healthcare, has given lectures in symposia sponsored by Biogen, Philips Nederlands, Esteve and Life Molecular Imaging and serves on an advisory board for Prothena Biosciences. R.S. has received personal consulting fees from Abbvie, AC Immune, Acumen, Alector, Bristol Myers Squibb, Janssen, Genentech, Ionis and Vaxxinity outside the submitted work. O.B. reported receiving personal fees from Adx NeuroSciences outside the submitted work. D.A. reported receiving personal fees for advisory board services and/or speaker honoraria from Fujirebio-Europe, Roche, Nutricia, Krka Farmacéutica and Esteve, outside the submitted work. A.L. has served as a consultant or on advisory boards for Almirall, Fujirebio-Europe, Grifols, Eisai, Lilly, Novartis, Roche, Biogen and Nutricia, outside the submitted work. J.F. reported receiving personal fees for service on the advisory boards, adjudication committees or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Perha, Roche and outside the submitted work. O.B., D.A., A.L. and J.F. report holding a patent for markers of synaptopathy in neurodegenerative disease (licensed to Adx, EPI8382175.0). The remaining authors declare no competing interests.

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Fortea, J., Pegueroles, J., Alcolea, D. et al. APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease. Nat Med (2024). https://doi.org/10.1038/s41591-024-02931-w

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Despite some moments that feel forced and overly earnest, particularly in the ancient narrative and the Nikitas story line, Landau’s writing is accessible, specific, lush and transporting. Her research is rigorous and full of elegant effort. The great success of this novel is the author’s sustained exploration of a woman in early midlife who, seething quietly on the inside but operating gracefully on the outside, bravely re-evaluates how her life has unfolded in order to progress as a mother to herself. Renderings of Ava’s childhood — a heartbreaking recollection of a favorite red belt, memories of a father’s girlfriend entering her life and then leaving it — are especially astute and rich.

At times, the novel’s disparate parts compete with rather than complement one another; some characters seem predictable, and certain ideas redundant. When things are meant to get weird, as in the rituals, it can feel more Scooby-Doo than genuinely haunting. For this reason, more than once, I felt like shaking the book like a snow globe, as if its fascinating contents, suspended, might set free more of its wildness.

Landau’s prose can also lift off the page, as it does in a prolonged memory of Ava’s first childbirth and its aftermath. Here, Landau’s writing is intimate, tender and full of terror. The sentences breathe with the softness of shared human experience across time — absolutely sufficient to the moment, and to eternity, too.

THE MOTHER OF ALL THINGS | By Alexis Landau | Pantheon | 336 pp. | $29

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