In a large-scale study of Hispanic and Latino adults, researchers at the University of California San Diego (UCSD) School of Medicine have discovered a link between self-reported cognitive decline and elevated levels of phosphorylated tau (ptau-181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) found in the blood. The findings, published in JAMA Network Open, indicate that the identified proteins could be the basis for a faster, less invasive, and less expensive diagnostic for Alzheimer’s disease and other related dementias.
“We need ways to identify underlying neurodegenerative diseases earlier in patients with cognitive symptoms,” said corresponding author Freddie Márquez, PhD, a postdoctoral researcher in the department of neurosciences at UCSD School of Medicine. “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.”
For their research, the UCSD team used the date of more than 5,700 Hispanic and/or Latino adults aged 50 to 86 from the Study of Latinos–Investigation of Neurocognitive Aging (SOL-INCA), which is a subset of the largest long-term study of Latino health in the U.S. Blood samples were analyzed for plasma concentrations of four key biomarkers: phosphorylated tau (ptau-181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-beta (Aβ42/40). Cognitive function was evaluated through participants’ self-reported concerns and the ECog-12, a validated questionnaire that captures perceived changes in memory and executive function.
Senior author Hector M. González, PhD, professor in the department of neurosciences at UCSD School of Medicine, highlighted the importance of researching this patient cohort: “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. Despite this, they’re still significantly underrepresented in Alzheimer’s and dementia research, which is something our study aimed to address.”
Analysis of the data showed that higher levels of ptau-181, NfL, and GFAP in the blood were associated with greater subjective cognitive decline (SCD), particularly in domains of memory and executive function.
Specifically, higher levels of ptau-181 were modestly associated with memory decline, while NfL was linked with perceived declines in overall cognitive performance, executive function, and memory. GFAP, a marker of neuroinflammation, was associated with declines in global cognition and executive function. Interestingly, the amyloid-beta marker Aβ42/40 showed no association with SCD in this population.
Further, among cognitively healthy individuals, the researchers also found associations between higher levels of NfL and self-reported cognitive decline indicating the NfL could be an early-warning biomarker of changes neurological health.
“Among cognitively unimpaired individuals, NfL was associated with subjective global, executive, and memory decline, raising the possibility that early neuroaxonal injury may play a role in perceived cognitive changes that precede overt cognitive impairment,” the researchers wrote.
Although there is currently one FDA-approved blood test for Alzheimer’s detection—the Lumipulse G pTau217/Aβ42 test—it remains expensive and limited to specialized care settings. The potential clinical implications of this study are considerable. The approach potentially offers a lower-cost and more accessible alternative to PET imaging or the use of cerebrospinal fluid for testing, both of which are more invasive and less practical for widespread use.
The UCSD researchers are now planning to conduct longitudinal analyses to determine whether these biomarkers predict objective cognitive decline or clinical Alzheimer’s diagnoses over time. Further research could also delve into how genetic, lifestyle, and environmental factors influence these biomarker patterns across diverse populations.
“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.”
