Researchers at the University of California, Los Angeles (UCLA) have identified a promising new blood-based biomarker that could help detect early brain changes linked to cognitive impairment and dementia. The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, demonstrates that elevated levels of placental growth factor (PlGF) in the blood may serve as an early indicator of vascular brain injury, potentially providing a cost-effective tool for screening patients at risk before significant cognitive decline occurs.
The research centers on cerebral small vessel disease (CSVD), a major driver of cognitive decline and dementia. CSVD is caused by dysfunctional cells lining blood vessels in the brain, leading to increased vascular permeability. Fluid and inflammatory molecules leak into brain tissue, causing injury that manifests as white matter hyperintensities (WMH) on MRI scans—bright spots that reflect structural damage. However, these imaging markers represent late-stage disease, often detected when cognitive symptoms are already underway.
The UCLA-led study shifts focus to earlier in the disease process by examining blood levels of PlGF, a protein critical for blood vessel formation but also linked to vascular permeability. “We found that plasma levels of this protein, placental growth factor (PlGF), could potentially be used as a biomarker to screen for and monitor cognitive impairment and dementia,” explained senior author Jason Hinman, MD, PhD, a vascular neurologist at UCLA Health.
Analyzing a diverse group of participants aged 55 and older, the researchers explored associations between PlGF levels, fluid accumulation in white matter (measured through a specialized MRI marker called free water), the development of WMH, and cognitive performance. The results supported a clear sequence: elevated PlGF levels correlated with greater vascular permeability, increased fluid accumulation, white matter injury, and, ultimately, cognitive decline.
“As a biomarker for cerebral small vessel disease and the vascular contributions to cognitive impairment and dementia (VCID), PlGF could be used as a cost-effective screening tool for identifying patients at risk for vascular brain injury before the insidious onset of cognitive decline,” said first author Kyle Kern, MD, also a vascular neurologist at UCLA Health. He emphasized that a simple blood test for PlGF could be invaluable for patients, clinicians, and researchers conducting clinical trials.
The study, part of the multisite MarkVCID consortium, included participants from diverse racial and ethnic backgrounds with varying vascular risk profiles. By analyzing both brain imaging and blood samples, the researchers established PlGF as a potential marker for early vascular brain injury, bridging a crucial gap between costly, late-stage MRI detection and early, accessible screening methods.
While these findings represent an exciting advancement, the authors noted that additional longitudinal studies are needed to confirm the timeline and causal relationships between PlGF, brain fluid accumulation, structural damage, and cognitive decline. Kern emphasized the potential for screening younger populations, stating that lifestyle changes and early interventions could “prevent or reverse the deleterious effects of vascular injury before the onset of cognitive dysfunction.”
By offering a noninvasive and cost-effective alternative to MRI, the PlGF blood test could revolutionize the early detection of vascular brain injury, providing patients and clinicians with valuable insights long before cognitive symptoms arise. As the research team continues recruiting patients for future studies, the hope is to bring this tool closer to clinical practice, enhancing early diagnosis and prevention of dementia-related diseases.
