The Dawn Study•Articles by: Anel Frederick

Author: Anel Frederick

PHLPP1 is highly concentrated in the baraOne Gene May Link Alzheimer’s Disease and Stroke

PHLPP1 is highly concentrated in the baraOne Gene May Link Alzheimer’s Disease and Stroke

In this study, we explored whether Alzheimer’s disease and stroke might share genetic causes in people with African ancestry. We found a region on chromosome 18 that appears to affect the risk for both conditions. When we looked more closely, we saw that this region interacts with a gene called PHLPP1, which may help explain why the two diseases sometimes occur together. PHLPP1 is highly concentrated in the brain so it makes sense that this gene is important in diseases which impact the brain. We also found that changes in this gene were linked to Alzheimer’s disease in a separate group of people with African ancestry. These findings were strongest for individuals with some African ancestry and whose PHLPP1 comes from Africa. This shows why it is important to study many different populations. When research includes everyone, we can discover risk factors that might be missed in studies focused only on people from one particular ancestry. Understanding these shared genetic links may help us find better ways to prevent or treat both conditions in the future.

Ray NR, Kurup J, Kumar A, et al. Genetic correlation analysis of Alzheimer’s disease and stroke implicates PHLPP1 as a shared locus in individuals of African ancestry. Alzheimers Dement. 2026 Apr;22(4):e71433. doi: 10.1002/alz.71433. PMID: 42043782; PMCID: PMC13116102.  

BIOMARKER

BIOMARKER

When you are studying or looking for the presence of a disease, there are several things a doctor or researcher would want to know. How is the part of the body that is affected by the disease functioning in that individual at this moment? One way would be to take a piece of heart or brain of the living patient and look at it, but obviously that is not something anyone wants to happen. What if there were tests that could give us information on the disease, but were not invasive or hurt the individual? These tests would measure abnormal changes elsewhere in the body that the disease was causing, providing information on the process of a disease in that individual. These indirect measurements of a disease process that are substitutes for direct measurements are called biomarkers.

Imaging, like CT, MRI or PET scans, are one kind of biomarkers for a disease process. While providing a lot of information these tests are expensive and not available to most individuals. If the disease affects the brain, then cerebrospinal fluid (CSF) can be drawn from a spinal tap. Many biomarkers can also be measured in a blood sample. Sometimes even urine can be used as a source of biomarkers.

Another important question in research is, can I predict if an individual is developing the disease before it causes symptoms? Many biomarkers can provide information that the disease has started before the person realizes it or has symptoms of the disease. If we can detect signs of the disease early, then we can do research with the goal to treat the disease early and possibly prevent symptoms from occurring at all.

Lastly, can we use this for development of new treatments? If you were testing a drug to treat a disease that progresses slowly over many years, you would want to know if it is working as soon as possible, rather than wait years to see if there are positive or negative results. If you measure the biomarkers many times during the disease, and they begin to return to their normal values, then you can know that the drug is working early in the trial.

Because of the value of biomarkers, the research improving them is a very active one. New biomarkers are being developed all the time. This is particularly true for blood biomarkers, as these are the easiest to obtain on an individual. Our studies include blood biomarkers, and some studies may also include imaging.

 

ABCA7 deletion lowers age at onset of Alzheimer’s disease and interacts with APOE ε4 synergistically in African-ancestry populations

ABCA7 deletion lowers age at onset of Alzheimer’s disease and interacts with APOE ε4 synergistically in African-ancestry populations

The APOE gene is the strongest known genetic risk factor for Alzheimer disease (AD), first identified by Dr. Pericak-Vance and colleagues in 1993. The ε4 allele of APOE, a version of the gene, increases the risk of AD and is associated with an earlier age at onset, although its effect differs across ancestries.

Another important gene is ABCA7, particularly in individuals of African ancestry.  We previously identified a deletion, or missing segment of DNA, in ABCA7 that is specific to African-ancestry populations and is associated with an increased risk of AD. Because APOE and ABCA7 are both involved in lipid metabolism, which is important for brain health, we wanted to understand whether these two genetic factors might work together to influence when AD begins.

To answer this question, we studied 3,510 individuals of African ancestry, including African American and African participants from the DAWN Research project. Bringing these groups together allowed us to examine the effects of the ABCA7 deletion within a broader, global African-ancestry population.

We found that individuals who carried both one copy of the APOE ε4 allele and the ABCA7 deletion developed AD earlier than individuals who carried one copy of APOE ε4 but did not carry the deletion. The difference was approximately five years. These findings suggest that APOE and ABCA7 may interact to influence the age at onset of AD. Studying this type of gene-gene interaction can help us better understand the biological mechanisms that contribute to the disease.

The study also highlights the importance of global participation in AD research. Studying populations globally allows us to gain a more comprehensive view of the genetic architecture of AD and a better understanding of the biological mechanisms underlying the disease. By including participants from both the United States and Africa, this study provided a broader perspective on how genetic factors influence AD. Continued global collaboration will be essential for advancing diagnosis, prevention, and treatment approaches that can benefit people across all populations.

Akgun B, Gulyayev AV, Coker M, et al. ABCA7 deletion lowers age at onset of Alzheimer’s disease and interacts with APOE ε4 synergistically in African-ancestry populations. Alzheimers Dement. 2025 Aug;21(8):e70583. doi: 10.1002/alz.70583. PMID: 40832784; PMCID: PMC12365657.

DAWN at AAIC London 2026

DAWN at AAIC London 2026

On Wednesday, July 15, Dr. Pericak-Vance co-chaired the session, “Global Population Studies Illuminate Alzheimer’s Disease Biology”, which highlighted findings made possible through DAWN’s global research approach.
 
Dr. Pericak-Vance introduced the session, and several DAWN investigators presented their work, including Dr. Rufus Akinyemi (University of Ibadan, Nigeria), Dr. Nicholas Ray (Columbia University), Dr. Biçag Akgün (presenting on behalf of Dr. Olabode Omotoso, University of Miami), and Dr. Aura Ramirez (University of Miami).
 
 

Education Helps Protect Thinking Skills

Education Helps Protect Thinking Skills

We studied how education relates to daily functioning in older Puerto Ricans who have high levels of a blood marker linked to Alzheimer’s disease. We found that people with more years of schooling had better functional abilities, even when they showed signs of higher Alzheimer’s-related protein levels. We also saw that each additional year of education lowered the chance of having problems with daily tasks. Although a genetic risk factor called APOE ε4 did not strongly change this pattern, there was a trend suggesting that education may help reduce some of the negative effects of this gene. These results suggest that education may help build “cognitive reserve,” which supports the brain when facing disease-related changes. Studying a diverse population like Puerto Ricans is important because it helps us understand how social and genetic factors work together in different communities. This work is significant because it shows that improving access to education may help protect brain health later in life.

Dorfsman DA, Cai D, Hamilton-Nelson KL, et al. Educational attainment is associated with reduced functional decline in Puerto Ricans with elevated pTau181. J Alzheimers Dis. 2026;110(2):685–695. doi:10.1177/13872877261415933

Differences in Ancestry Affect the APOE ε4 Gene and Alzheimer’s Disease Risk

Ancestry-related Differences in Chromatin Accessibility and Gene Expression of APOE ε4 Are Associated with Alzheimer’s Disease Risk

In this study, we explored why the APOE ε4 gene increases Alzheimer’s disease risk more strongly in people with European ancestry than in those with African ancestry. We analyzed brain tissue from individuals with Alzheimer’s disease who all carried two copies of APOE ε4 but differed in their local genetic ancestry around the APOE gene. Our results showed that APOE ε4 was more active in brains with European local ancestry, especially in astrocytes, a type of support cell in the brain. We found that this increased activity was linked to greater chromatin accessibility, meaning the DNA near APOE ε4 was more open and easier to turn on in European ancestry brains. These ancestry-related differences were not limited to APOE alone but extended across the genome. Genes with increased accessibility in European ancestry astrocytes were involved in processes such as synaptic function, cholesterol handling, and astrocyte reactivity. In the discussion, we suggest that these molecular differences help explain why APOE ε4 confers higher Alzheimer’s disease risk in people with European ancestry compared to those with African ancestry. Our findings highlight that genetic risk depends not only on which variant a person carries, but also on ancestry-specific regulation of gene activity. This work underscores the importance of studying multiple ancestries to fully understand Alzheimer’s disease biology and to ensure that genetic insights are relevant to all populations

Rajabli F, Seixas AA, Akgun B, Adams LD, Inciute J, Hamilton KL, Whithead PG, Konidari I, Gu T, Arvizu J, Golightly CG, Starks TD, Laux R, Byrd GS, Haines JL, Beecham GW, Griswold AJ, Vance JM, Cuccaro ML, Pericak-Vance MA. African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer’s Disease Measured by pTau181. J Alzheimers Dis. 2024;98(1):221-229. doi: 10.3233/JAD-231116. PMID: 38393909; PMCID: PMC11091636.

African Ancestry Individuals with More Education Show Greater Resistance to Alzheimer’s Disease, Based on pTau181 Levels

African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer’s Disease Measured by pTau181

In this study, we examined why some African ancestry individuals show better daily functioning even when they have biological signs of Alzheimer’s disease. We focused on a blood biomarker called pTau181, which reflects Alzheimer’s disease pathology in the brain. Our results showed that African American individuals with higher levels of education were better able to carry out everyday activities, even when their pTau181 levels were high. This suggests that education may help protect against the functional effects of Alzheimer’s disease, a concept often called cognitive or brain reserve. We also found that this protective effect of education was stronger in people who did not carry the APOE ε4 genetic risk factor. In the discussion, we suggest that education may help the brain cope with disease-related changes, delaying or reducing functional problems. These findings highlight that social factors, like access to education, play an important role in Alzheimer’s disease outcomes. Studying African ancestry populations is especially important because most Alzheimer’s research has focused on European ancestry groups, which can miss important differences. We conclude that including diverse ancestries and life experiences in research is essential for understanding resilience to Alzheimer’s disease and for developing more equitable prevention and care strategies.

Rajabli F, Seixas AA, Akgun B, Adams LD, Inciute J, Hamilton KL, Whithead PG, Konidari I, Gu T, Arvizu J, Golightly CG, Starks TD, Laux R, Byrd GS, Haines JL, Beecham GW, Griswold AJ, Vance JM, Cuccaro ML, Pericak-Vance MA. African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer’s Disease Measured by pTau181. J Alzheimers Dis. 2024;98(1):221-229. doi: 10.3233/JAD-231116. PMID: 38393909; PMCID: PMC11091636.

 

AD Plasma Biomarker Stability at −20°C in Resource-Constrained Settings

Exploring the stability of AD plasma biomarkers stored for extended periods at −20°C: Implications for resource-constrained environments

In this study, we wanted to see if blood markers linked to Alzheimer’s disease stay stable when stored for a long time at -20°C, a temperature many labs around the world can access. We found that these biomarkers, including those related to amyloid and tau, did not change much over time, even without ultra-cold freezers. This means that labs with fewer resources can still collect and store samples in a reliable way (up to 15 weeks).These results show that important Alzheimer’s research does not always require expensive equipment. Because of this, more communities and countries can take part in studies that help us understand the disease. This makes research more fair and more representative of people around the world. Our findings could help improve early testing and tracking of Alzheimer’s disease in places that have been left out before. Overall, this work supports better access to scientific tools and helps move Alzheimer’s research forward in a more inclusive way.

Ayele BA, Whitehead PL, Pascual J, et al. AD plasma biomarkers are stable for an extended period at -20°C: implications for resource-constrained environments. Preprint. medRxiv. 2024;2024.07.17.24310504. Published 2024 Jul 17. doi:10.1101/2024.07.17.24310504

Mining DNA for Alzheimer’s Secrets

Mining DNA for Alzheimer’s Secrets


By Josh Baxt

Researchers at the John P. Hussman Institute for Human Genomics (HIHG) at the University of Miami Miller School of Medicine are uncovering new insights into the genetic roots of Alzheimer’s disease, the most common form of dementia. Led by Anthony Griswold, Ph.D., and Brian Kunkle, Ph.D., M.P.H., the team is using advanced genome-wide association studies and whole-genome sequencing to identify genetic variations that influence risk and protection against the disease.

Their work casts a global net beyond populations of European ancestry to include groups from Africa, the Caribbean, and South America, revealing unique genetic markers and protective factors, such as variants in the APOEΣ4 gene. These discoveries are helping researchers better understand disease mechanisms and uncover new therapeutic targets.

The HIHG team is also advancing early detection efforts through innovative “liquid biopsy” techniques that identify Alzheimer’s biomarkers in blood plasma. This approach could allow for earlier diagnosis and more personalized treatment strategies.

“Every time we bring in a new population we’ve never studied before, we find new genetic markers,” said Dr. Griswold. “That’s going to help us develop diagnostic tests and medicines that could eventually help all people with Alzheimer’s.”

For the full story, click here.

🧠 Want a Healthier Brain? Try Being Creative!

🧠 Want a Healthier Brain? Try Being Creative!

By Susan H. Blanton, Ph.D.

A new study shows that doing creative things—like dancing, painting, playing music, or even playing video games—can help keep your brain younger and healthier.

Scientists looked at brain scans from over 1,400 people and used computers to figure out their “brain age.” That’s how old your brain seems based on how it works. They found that people who do creative activities often had brains that looked younger than their real age.

Even learning something new for a short time, like playing a strategy video game, helped. But the biggest benefits came from people who had been doing creative things for many years.

The study also found that creativity helps the brain stay strong in areas that usually get weaker with age. It improves how different parts of the brain work together, which helps with thinking, memory, and focus.

The best part? These benefits were seen in people from all over the world, no matter what kind of creative activity they did.

So if you want to keep your brain sharp, try something creative! Whether it’s dancing, drawing, or gaming, your brain will thank you.

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