Study could pave the way for simple blood test to diagnose Alzheimer's disease

In a landmark study of Hispanic and Latino adults, researchers at University of California San Diego School of Medicine have identified a link between self-reported cognitive decline and blood-based biomarkers, which could pave the way for a simple blood test to help diagnose Alzheimer's disease and related dementias. This approach could be faster, less-invasive and more affordable than existing screening tools. The results are published in JAMA Network Open.

We need ways to identify underlying neurodegenerative diseases earlier in patients with cognitive symptoms. This study highlights the promise of blood-based biomarkers as a more accessible and scalable tool for understanding cognitive decline, particularly in populations that have been underserved by traditional methods."

Freddie Márquez, Ph.D., corresponding author, postdoctoral scholar, Department of Neurosciences, UC San Diego School of Medicine

There is currently only one blood test approved by the Food and Drug Administration to assist in diagnosing Alzheimer's disease. While this test, the Lumipulse G pTau217/Aβ42 plasma ratio, can detect proteins associated with Alzheimer's in the blood, it is currently very expensive and only available in specialized care settings. Whether or not blood can be reliably used for early Alzheimer's detection on a larger scale is still unknown.

To help answer this question, the researchers used data from the Study of Latinos–Investigation of Neurocognitive Aging. This clinical study assessed neurocognition in a subset of participants from the Hispanic Community Health Study/Study of Latinos, the largest, most comprehensive long-term study of Hispanic and Latino health and disease in the United States.

"Hispanic and Latino adults are thought to be more likely to get Alzheimer's and related dementias, and this group is projected to have the largest increases in disease prevalence over the coming decades," said senior author Hector M. González, Ph.D., professor in the Department of Neurosciences at UC San Diego School of Medicine. "Despite this, they're still significantly underrepresented in Alzheimer's and dementia research, which is something our study aimed to address."

The researchers tested the blood of 5,712 Hispanic and/or Latino adults between the ages of 50 and 86, looking for proteins that are present in the brain in people with Alzheimer's disease, such as amyloid beta and tau proteins. They also assessed participants for subjective cognitive decline, which refers to a decline in cognitive status that the individual themself perceives.

The researchers found:

• Higher blood levels of NfL (nerve cell injury marker) and GFAP (brain inflammation marker) were associated with more self-reported declines in thinking, planning and overall cognitive performance. Higher blood levels of NfL and tau protein (ptau-181) were also associated with more self-reported declines in memory.
• Blood levels of amyloid-beta protein (Aβ42/40), a protein well-known to be associated with Alzheimer's disease in the brain, showed no associations with subjective cognitive decline.
• Even in cognitively healthy individuals, associations between NfL and self-reported declines in cognitive performance remained, suggesting that NfL may be detecting early changes in cognition.

In addition to providing evidence that blood-based biomarkers can be used to detect Alzheimer's and related dementias early, the researchers also note that a strength of their study is its diverse population.

"By including participants from underrepresented communities, we're able to better understand how social determinants of health and comorbidities may influence cognitive trajectories and dementia risk," added Márquez. "This makes our findings especially relevant for real-world settings."

However, the researchers also caution that it will take further research for this approach to make its way into widespread clinical practice, and that even when this happens, the test will still be just one tool in a clinician's diagnostic arsenal.

It's important to note that there's still a lot we don't know about the utility of blood-based biomarkers for Alzheimer's detection," said Márquez. "These tests have tremendous potential, but they should complement existing approaches, not replace them."

Additional coauthors of the study include Kevin Gonzalez, Deisha F. Valencia and Natasha Z. Anita at UC San Diego, Wassim Tarraf at Wayne State University, Ariana M. Stickel and Linda C. Gallo at San Diego State University, Daniela Sotres-Alvarez and Haibo Zhou at University of North Carolina at Chapel Hill, Bonnie E. Levin and Zachary T. Goodman at University of Miami, Michael A. Yassa at UC Irvine, Martha Daviglus and Amber Pirzada at University of Illinois at Chicago and Bharat Thyagarajan at University of Minnesota.

This study was funded, in part, by grants from the National Institute on Aging (R01AG075758). The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a collaborative study supported by contracts from the NHLBI to the University of North Carolina (grant Nos. HHSN268201300001I/N01-HC-65233), University of Miami (grant Nos. HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (grant Nos. HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (grant Nos. HHSN268201300003I/N01- HC-65236 Northwestern University), and San Diego State University (grant Nos. HHSN268201300005I/N01-HC-65237).