Untangling Alzheimer’s: ASU researchers tackling our understanding of the disease on many fronts

Among the major causes of death, Alzheimer’s disease is a striking outlier. 

Deaths from other leading killers — including heart disease, stroke, cancer and HIV — declined significantly between 2000 and 2019. But deaths from Alzheimer’s disease in the U.S. increased by about 145%, according to the Alzheimer’s Association.

The figures partly reflect improved diagnosis of Alzheimer’s disease and an aging population. Yet the data are also a reminder of just how challenging it has been to fully comprehend a disease of such complexity, which causes a baffling array of symptoms. Despite enormous efforts and billions of dollars invested in research, the shadowy illness still has no effective treatment or cure.

The tides may be turning, however. Research advances are beginning to fit the many puzzle pieces of Alzheimer’s disease into a coherent picture, offering new hope for patients and their families.

At Arizona State University’s ASU-Banner Neurodegenerative Disease Research Center, or NDRC, scientists are working on many fronts to try to crack the code of this devastating illness. Their research is finding new connections between our environment and Alzheimer’s. And it offers a unifying explanation for these connections — one that may offer new avenues for treatment.

“The NDRC is incredibly excited by the advances we've made in the area of Alzheimer's disease, especially on preclinical models,” says Jeff Kordower. “In the future, we're looking forward to expanding our interests to include other diseases of cognition, such as frontotemporal dementia and Lewy body disease, and this will be a major effort for the NDRC in coming years.”

Kordower directs the NDRC and is a professor with the School of Life Sciences at ASU. 

If you could peer inside a brain with advanced Alzheimer’s, the first thing you’d notice is shrinkage — whole regions thinning and withering, like forests stripped bare. But the devastation begins long before such visible signs appear. 

For decades, the disease works in silence, degrading the brain from within.

Alzheimer’s often begins in areas of the brain that are critical for memory. Here, sticky amyloid plaques begin to form, and tau proteins twist into toxic tangles. These changes are closely linked with the loss of synaptic connections — the networks that support thought, memory and perception. 

The brain’s wiring begins to fail, often years before symptoms appear. As damage spreads through the cerebral cortex, it erodes language, judgment and eventually the ability to recognize loved ones. 

What if part of the key to slowing Alzheimer’s was already on your plate? Recent research at NDRC suggests choline, an essential nutrient, may play a role in protecting the brain.

Scientists examined blood samples from people across the Alzheimer’s spectrum — from mild cognitive impairment to full-blown disease. They found that lower choline levels corresponded with higher amounts of both amyloid plaques and tau tangles, hallmarks of the disease. The lower the choline, the worse the brain looked under the microscope. They also found that lower choline was linked to higher levels of TNF alpha, a marker of inflammation, and to poorer performance on memory and thinking tests.

Most people don’t get enough choline in their diet. Estimates suggest that around 90% of Americans fall short of recommended levels. The findings raise the possibility that increasing choline intake — whether through diet or supplements — could lower Alzheimer’s risk or slow its advance.

More testing is needed, but measuring choline in the blood might one day help identify Alzheimer’s risk or progression. More broadly, this research underscores the idea that diet deserves more attention in the fight against neurodegeneration.

A growing number of pollutants in our environment are being linked to neurodegenerative disease. One of these is glyphosate, a common weed killer used in agriculture and landscaping worldwide.

New research suggests that even short-term glyphosate exposure may cause lasting harm to the brain. 

ASU researchers studied both high and low doses of glyphosate. Both levels produced measurable changes in brain tissue, suggesting that even the accepted human threshold may not be safe. Researchers also found evidence that glyphosate byproducts linger in the brain long after exposure, potentially continuing to interfere with brain health.

More research is needed to understand how these findings translate to humans. People who work with glyphosate, including farmworkers and landscapers, may be at higher risk. But the chemical has also been detected in trace amounts in food and water that we all consume.

“Given the increasing incidence of cognitive decline in the aging population, particularly in rural communities where exposure to glyphosate is more common due to large-scale farming, there is an urgent need for more basic research on the effects of this herbicide,” said lead researcher Ramon Velazquez.

For decades, Alzheimer’s researchers have focused on the brain. But what if part of the story begins in the gut? 

That’s the question raised by a striking new study, which suggests that a common viral infection in the intestines may play a hidden role in the development of Alzheimer’s disease — at least in some people.

“We think we found a biologically unique subtype of Alzheimer’s that may affect 25% to 45% of people with this disease,” said Associate Research Professor Ben Readhead, co-first author of the study. 

The culprit is cytomegalovirus, or HCMV — a usually harmless member of the herpes virus family. Most of us carry it for life without even knowing it. But in some individuals, researchers found, the virus may remain active in the gut and eventually creep upward along the vagus nerve — the body’s information superhighway between belly and brain.

The team estimates that 25% to 45% of cases may involve this viral-driven pathway. That opens the possibility of targeted treatments — perhaps even antiviral drugs already on the market, for a specific subtype of the disease.

ASU has received new funding from the Arizona Alzheimer’s Consortium to investigate a possible link between microplastics and neurodegeneration. 

A collaborative effort with ASU, the University of Wisconsin-Madison, the Banner Sun Health Research Institute, Rush University Medical Center and the Banner Alzheimer’s Institute, it is one of the first to test whether tiny plastic particles accumulate in the brain and contribute to Alzheimer’s disease.

The team will study brain and spinal fluid samples from well-documented donors, using resources from the Banner Sun Health Brain and Body Donation Program. They will also incorporate neighborhood-level socioeconomic data to explore how social and environmental factors may influence brain health.

By linking environmental exposures with brain pathology and health disparities, the project positions ASU at the forefront of an important new field — environmental brain health. Findings could identify microplastics as a novel risk factor for dementia, guide prevention strategies and improve public health policies.

There are many neurodegenerative diseases, but they seem to share common roots. An NDRC study suggests that Alzheimer’s, Parkinson’s, ALS, Huntington’s, frontotemporal dementia and Friedreich’s ataxia all carry common signs at the cellular level — along with unique features.

To uncover these patterns, researchers studied RNA in blood samples. They used machine learning to identify gene activity signals that distinguish people with each disease from those without it. Then, they asked: Which disrupted cellular processes appear across diseases, and which are specific to just one?

They found eight core cellular malfunctions that recur in all six diseases. These include problems with how cells manage proteins, regulate RNA transcription, respond to inflammation, produce energy, undergo cell death and maintain their internal structure. In other words, many diseases may arise from breakdowns in the same basic cellular machinery.

But each disease also had its own fingerprint. For example, only Alzheimer’s showed changes in the machinery that helps process RNA messages. These distinct patterns might help explain why each disease targets different brain regions and causes different symptoms.

“It appears that multiple neurodegenerative diseases harbor similar fundamental dysfunctional cellular processes,” Assistant Research Professor Carol Huseby said. “Differences between diseases may be key to discovering regional cell-type vulnerabilities and therapeutic targets for each disease.” 

Another study takes a holistic view, tying together many distinct Alzheimer's findings gathered over decades of research. It also connects these biological changes to known risk factors — including aging, genetics, viral infections and more.

The researchers suggest that Alzheimer’s begins when cells fail to respond properly to stress. In healthy brains, cells handle stress by adjusting gene activity, shutting down unnecessary functions and protecting key processes. But in Alzheimer’s, this response system seems to break down. These stress-related failures lead to changes in the activity of thousands of genes — a ripple effect that disrupts many of the brain’s vital systems.

Importantly, the model doesn’t focus on just one cause. It offers a unifying explanation for how many different risk factors — from aging and genetics to viral infections, environmental toxins and nutrient deficiencies — could all set off the same chain of events. 

If scientists can find ways to restore healthy stress responses in brain cells, they may be able to slow or prevent the damage, according to Research Professor Paul Coleman, who led the research.

“Studying these early manifestations of Alzheimer's could pave the way for innovative approaches to diagnosis, treatment and prevention, addressing the disease at its roots," Coleman said.