DIAN EXR Newsletter: Vol. 7, Issue 1

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We Are All Connected: Davide’s Story

I’m pleased to open the first issue of 2025 by sharing my delightful chat with Davide Mangani, who has lost family members to DIAD. In their memory, he is embarking on the Swiss Man Extreme Triathlon. We talked about his training regimen, what inspires him, and how he copes when things get difficult. (This interview has been lightly edited for length and clarity.)

Jamie Bartzel: How would you like to introduce yourself?

JB: Tell me about your project.

If I can dedicate myself to complete such a challenge … I will be able to face anything that life throws at me. … Nothing will bring back my dad and uncle, but I will have the strength to honor them every day. I try to convey the message that if we act, take care of our families, help other people, help each other out, do something—not just say, “Life has given me all this sorrow, all this pain; I cannot go forward.” Whatever motivates you to get out of your comfort zone—it doesn’t matter what—just do it. 

JB: Which is harder: the mental journey or the physical challenges?

DM: The mental part is much harder. Sometimes, when I start to work out, especially in the beginning, I feel really overwhelmed. But after two or three hours, when I think I should feel more tired, I feel alive, because my mind clicked—it embraced the challenge. … Of course, you need to train smart and avoid injuries, but the real message is that you have to have your mind ready for it. 

JB: What are your training strategies?

DM: The first phase is preparation. You need to have a schedule. It’s very important to make it a habit, the same way we brush our teeth. The training schedule has to be in our agenda … in a way that becomes a habit, and then you do it because of inertia. Maybe not so exciting, but it makes you stick to the plan. 

The second part … I always train without any music or podcasts; I just stay with my brain. … You have to learn how to lead with your mind. … We need to meet with our mind and listen to it, and cope with it. Sometimes I have ideas, or sad feelings, and I just let my mind be my mind. I am kind of a spectator. I’m learning so much about my brain and how it works.  

JB: And what unexpected joys have you found during your training process?

DM: I realize that it’s not so bad to be in my mind. I’m enjoying listening to my mind—I recognize that it’s me. I hadn’t met this person yet. The other joy is that … when I run or bike in the mountains, [I see] the scenery, the trees, the light during the day. [I have a] connection with nature; it brings an ancient feeling that we are part of this.

JB: It sounds like you’re really grounded in love: for yourself, and for nature.

DM: In the moment you start to love yourself, you recognize yourself as a part of nature.

JB: What else keeps you grounded?

DM: I have started meal planning. I am trying vegetables and fruits, learning a lot about nutrition, and learning how to preserve and maintain my body with healthy habits. I’ve met a lot of people in training, who are really invested in these sports, and everyone has their own motivation. Despite my family story, I feel lucky. I was born in a peaceful country, there was no war or famine, and I feel lucky for everything around me.  

JB: How do you cope when you feel sad about the losses in your family?

DM: When I think about how much I miss my dad—he used to play the guitar in a blues band, and I replay his voice singing in my mind. His voice is still there; it’s almost like I’m hearing it.  

JB: Is there anything else you would like to share?

DM: To other [DIAD] families: we know firsthand what it means to see the people we love suffer, so … it’s very rare to see the good part of life, the joys we can still have despite everything. Reach out to me or others in the community. When you share, when you talk, you are unloading weight from yourself. Then you have space to load the joy.

To the general public: this disease exists and is devastating. Often, families don’t talk about it because of shame or not wanting to share the sorrow they experience. Ask the people you know, “How are you? Is there anything I can do?” It really goes far. … If you can contribute to charity or to research … then that would be amazing.  

I would like this journey to be interactive. I want people to reach out, ask questions, and share how they cope with other struggles in life: cancer, depression, financial problems. Everyone has pain and sorrow. Coping mechanisms can be shared across different communities. We are all connected.  

Find Davide on Instagram, and follow his training journey on YouTube.

WashU Community Support for the Primary Prevention Trial

To help bring the promising research of the DIAN-TU to fruition, longtime university benefactor Joanne Knight established the Knight Alzheimer’s Primary Prevention Challenge. Her gift, as well as additional donations secured as part of a $6.5 million matching challenge, will help support the primary prevention trial design and implementation.

To date, over 170 individuals and organizations have contributed more than half of the $6.5 million goal for the challenge. Gifts are matched dollar-for-dollar until the goal is met. The collective power of the Knight Challenge has played a critical role in allowing the DIAN-TU to design flexible, nimble trials. The challenge is a testament to the critical impact philanthropy has on driving scientific progress.

If you know anyone who would be interested in learning more about the Knight Challenge and ways to support the DIAN-TU, please contact Emily Wozniak, Executive Director of Medical Advancement by phone (+1 314-973-6479) or email (wozniake@wustl.edu).

Save the Date: Webinar for DIAD Family Members and Caregivers

The DIAN Expanded Registry will host a webinar question-and-answer session on research funding on Saturday, April 12, from 3:00 – 4:00 PM CDT / 21:00 BST; 6:00 AEST 13APR. Dr. Randall Bateman will provide updates on current research funding and answer questions. The webinar will be offered in English, and a recording will be posted to our website shortly after the event.

This webinar is for DIAD family members and caregivers only. If you are a person with or caregiver for someone who has or is at risk for a DIAD mutation and did not receive an email invitation to this webinar from the DIAN Expanded Registry, please email dianexr@wustl.edu.

2025 DIAD Family Conferences and Meetings

Registration has opened for the global 2025 DIAD Family Conference! We will gather on Saturday, July 26 in Toronto, Canada. This event will bring together DIAD family members and caregivers from across the globe. If you are a member of a DIAD family and would like more information about registration, email dianexr@wustl.edu.

A regional conference will be held in Sydney, Australia on Thursday, May 29, 2025, for DIAD family members and caregivers from Australia and New Zealand. For more information on the Australian conference, email Emily Kerameas at anz-diadconference@neura.edu.au.

A regional conference focusing on DIAD will also be hosted by Alzheimer Center Amsterdam in Amsterdam, Netherlands, on April 12, 2025. Families from the Netherlands and Belgium are warmly invited to attend. To learn more, email Ghiselinde Meijs at g.meijs@amsterdamumc.nl.

Primary Prevention Launch

The first participants in an international clinical trial aimed at preventing Alzheimer’s disease in young adults at high risk of the disease have been enrolled. The trial, led by Washington University School of Medicine in St. Louis, aims to determine whether stopping the early molecular changes that lead to symptomatic Alzheimer’s disease can prevent the disease from ever taking hold. The study is enrolling people as young as 18 who have few or no detectable Alzheimer’s-related molecular changes in their brains, up to 25 years before the expected onset of dementia symptoms.

While the trial is limited to members of families with genetic mutations that all but guarantee they will develop Alzheimer’s at a young age, typically in their 30s, 40s or 50s, the researchers expect that the study’s results will inform prevention and treatment efforts for all forms of Alzheimer’s disease.

Called the Primary Prevention Trial, the new study investigates whether remternetug—an investigational antibody being developed by Eli Lilly and Company—can remove plaques of a key Alzheimer’s protein called amyloid beta from the brain or block them from accumulating in the first place. Both genetic and nongenetic forms of Alzheimer’s disease start with amyloid slowly collecting in the brain two decades before memory and thinking problems arise. By clearing out low levels of amyloid beta plaques or preventing them from accumulating during the early, asymptomatic phase of the disease, or both, the researchers hope to interrupt the disease process at the earliest stage and spare people from ever developing symptoms.

“We have seen tremendous progress in the treatment of Alzheimer disease in the past few years,” said Eric McDade, DO, a professor of neurology and the trial’s principal investigator. “Two amyloid-targeting drugs were shown to slow symptoms of the disease and have now been approved by the Food and Drug Administration (FDA) as treatments for people with mild cognitive impairment or mild dementia due to Alzheimer’s disease. This provides strong support for our hypothesis that intervening when amyloid beta plaques are at the very earliest stage, long before symptoms arise, could prevent symptoms from emerging in the first place.”

Read more about Primary Prevention at https://medicine.washu.edu/news/international-alzheimers-prevention-trial-in-young-adults-begins/ If you are interested in learning more about available study locations and/or joining the clinical trial, please join the DIAN Expanded Registry.

DIAD Family Planning and Primary Prevention Fertility Guide

Many members of DIAD families consider how and whether to have children, and if they should take steps to minimize a potential child’s risk of inheriting a DIAD genetic mutation. These considerations are unique to families that deal with rare genetic disorders, and resources around this topic are often scarce (or nonexistent).

One factor that also affects clinical trial participation is fertility. Often, a condition of joining a clinical trial (of any type) is agreeing not to become pregnant during the trial—as is required for the Primary Prevention trial (DIAN-TU-002). This leaves potential trial participants wondering what their options are if they wish to have children.

The DIAN-TU and Expanded Registry partnered with Youngtimers co-founder Dr. Lindsay Hohsfield to develop a fertility guide that provides steps to help navigate family planning considering DIAD risk and clinical trial participation. We break down different considerations so individuals can make the best decisions according to their unique circumstances—including a high-level overview of what the Primary Prevention trial involves, what fertility preservation is, and different reproductive options for people at risk for DIAD. The full guide is available at https://dian.wustl.edu/items/fertility-guide.

We are grateful to the following individuals for their contributions to this guide: a participant advisory group (young adults at-risk of DIAD and eligible for the Primary Prevention Trial); Katie Neimeyer, MS, CGC, a genetic counselor; and Dr. Laxmi Kondapalli, MD, a board-certified reproductive endocrinologist and infertility specialist. 

Our Research in the News

• A Man Fated to Get Alzheimer’s Avoided It For Decades. But How?
• Can a Drug Prevent Alzheimer’s Disease Decades Before It Happens?
• Small study hints anti-amyloid therapy may keep Alzheimer’s symptoms at bay in certain patients
• Researchers find a hint at how to delay Alzheimer’s symptoms. Now they have to prove it
• Study shows drug may prevent Alzheimer’s. NIH slowdowns threaten future research

DIAN Observational Study Data at the Rare Disease Symposium

In celebration of Rare Disease Day, WashU hosted the 3rd Annual Rare Disease Day Symposium on February 20, 2025, with invited guests that included researchers, students, advocacy groups, affected individuals and their family members. While many of the posters and talks focused on pediatric diseases, I found this an excellent opportunity to share information learned from the more than 15 years that the DIAN Observational Study, DIAN-Trials Unit, and DIAN Expanded Registry have worked with DIAD individuals and families. I also believe that I could learn from other groups about research strategies, advocacy, and developing empathy while focusing on hope. I was not disappointed, as the session began with three excellent speakers from advocacy groups including Siblings with a Mission, Cystic Fibrosis Foundation, and June Jessee Memorial Foundation, followed by an overview of the development of genomic medicine program by the director of the National Human Genome Research Institute at NIH, Eric Green.

While the WashU Rare Disease Day Symposium is much smaller than other scientific meetings, it was a wonderful opportunity to talk with others in the field about working with rare diseases, which is much more focused on individuals than common disease research. It was energizing to see the passion everyone expressed. While many of the later research talks and posters included technical details with which few had experience, we all shared the sense of urgency and discovery that, even though focused on specific rare disease, can bring broader understanding to human health and disease. We left the symposium with an enthusiasm for finding other similar opportunities to talk about DIAN and to contribute more fully during next year’s observance of Rare Disease Day.

—Laura Courtney, Manager of Division Clinical Research, DIAN Observational Study

Family Resource: Video on Grief and Loss

The Knight Alzheimer’s Disease Research Center presented a webinar on Grief and Loss in Dementia Care, led by Jennifer K. Phillips, MPA, in February 2025. This presentation discussed the unique path of grief traveled by both people with dementia and those who love them. A recording can be accessed at https://vimeo.com/1056875282/26d99db848.

Recent DIAN Publications

Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer’s disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial

Depressive Symptoms and Amyloid Pathology

Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia

The landscape of autosomal-dominant Alzheimer’s disease: global distribution and age of onset

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease

Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer’s disease

For a full list of publications using DIAN Obs and DIAN-TU data, visit PubMed.

DIAN Obs and DIAN-TU data are increasingly published in scientific reports to advance scientific understanding of Alzheimer’s disease. There is a marginal risk that a participant reading or hearing of these scientific reports might guess, correctly or incorrectly, information including their own or a family member’s mutation or treatment status. We take every step to minimize this risk, including ensuring that all study data lack identifying information, but de-identified data may reveal a pattern suggesting a person’s mutation or treatment status. Avoid articles or presentations related to our studies to decrease this risk.

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If you are interested in research opportunities,
contact the DIAN Expanded Registry at dianexr@wustl.edu.