UCLA researchers have identified placental growth factor (PlGF) as a potential blood biomarker for early detection of cognitive impairment and dementia.
High PlGF levels correlate with increased vascular permeability, suggesting its role in the development of cerebral small vessel disease. This finding could enable earlier identification and intervention for at-risk individuals compared to current MRI-based diagnostics.
Vascular Changes and Dementia
Researchers and clinicians typically use MRI scans to track brain blood vessel changes linked to cognitive impairment and dementia. These scans detect “downstream” biological markers — signs that appear later in the disease process. However, a multicenter study led by UCLA researchers suggests that a simple blood test could spot earlier changes, potentially identifying at-risk patients sooner and at a lower cost.
“We studied a protein in the blood that is critical in the formation of blood vessels but that also appears to play a role in vascular permeability associated with cognitive decline,” explained Jason Hinman, MD, PhD, a vascular neurologist at UCLA Health, Interim Co-Director of the Mary S. Easton Center for Alzheimer’s Research and Care at David Geffen School of Medicine at UCLA and senior author of an article in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Evaluating data from a large group of patients with a range of vascular risk profiles and cognition ranging from unimpaired to mild dementia, 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.”
Cerebral Small Vessel Disease and Biomarkers
Dysfunctional cells lining blood vessels in the brain are increasingly recognized as a key driver of processes leading to cerebral small vessel disease (CSVD), a major contributor to cognitive decline and dementia. The leaky vessels are believed to allow fluid and inflammatory molecules to seep into brain tissue. CSVD is typically diagnosed through costly brain MRI, where areas of vascular-mediated brain injury appear as bright spots on clinical MRI sequences – called white matter hyperintensities, or WMH. WMH and other structural changes are late markers of vascular brain injury.
Potential of PlGF as a Biomarker
The researchers studied possible associations involving several factors: plasma levels of PlGF, a highly sensitive research MRI measure of fluid accumulation in the brain called white matter free water (FW), white matter hyperintensities, and patients’ scores on cognitive assessments. Results were consistent with models suggesting that elevated PlGF increases vascular permeability, leading to accumulation of fluid in the brain’s white matter, development of white matter hyperintensities, and subsequent cognitive impairment.
“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, a vascular neurologist at UCLA Health and researcher at David Geffen School of Medicine at UCLA. “As a simple blood test, such a tool would be valuable not only for patients and clinicians, but also for researchers identifying patients for clinical trials,” he said.
Study Design and Future Directions
The study was conducted by researchers involved in MarkVCID, a multisite consortium established to validate candidate biomarkers for CSVD through recruitment of participants from diverse racial and ethnic backgrounds, with a range of vascular risk factors, and across the spectrum of cognitive impairment. Participants were 55 or older and had undergone brain MRI and blood tests for PlGF levels.
The authors said that while the study’s multicenter design and large, diverse sample support the use of PlGF as a biomarker, additional longitudinal studies are needed to reach conclusions about causation and timing in the relationships among PlGF, FW, WMH, and cognition. Ideally, PlGF could be used to screen younger populations for whom currently available treatments and lifestyle modifications may prevent or reverse the deleterious effects of vascular injury before the onset of cognitive dysfunction. The research group is recruiting patients for future studies.
Reference: “White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status” 18 December 2024, Alzheimer’s & Dementia.
DOI: 10.1002/alz.14408
Funding: National Institutes of Health, Grant/Award Numbers: U24NS100591, UH2NS100599, UH2/UH3NS100605, UH2NS100588, UH2NS100608, UH2NS100606, UH2NS100598, UH2NS100614, UF1NS125513, the BrightFocus Foundation.
News
Simple Blood Test To Detect Dementia Before Symptoms Appear
UCLA researchers have identified placental growth factor (PlGF) as a potential blood biomarker for early detection of cognitive impairment and dementia. High PlGF levels correlate with increased vascular permeability, suggesting its role in the development [...]
Investing Goldman Sachs asks ‘Is curing patients a sustainable business model?’
Goldman Sachs analysts attempted to address a touchy subject for biotech companies, especially those involved in the pioneering “gene therapy” treatment: cures could be bad for business in the long run. “Is curing patients [...]
The risks of reversed chirality: Study highlights dangers of mirror organisms
A groundbreaking study evaluates the feasibility, risks, and ethical considerations of creating mirror bacteria with reversed chirality, highlighting potential threats to health and ecosystems. In a recent study published in Science, a team of researchers [...]
Alarming Mutation in H5N1 Virus Raises Pandemic Red Flags
NIH-funded study concludes that the risk of human infection remains low A recent study published in Science and funded by the National Institutes of Health (NIH) has found that a single alteration in a protein on the surface [...]
Scientists Discover Genetic Changes Linked to Autism, Schizophrenia
The Tbx1 gene influences brain volume and social behavior in autism and schizophrenia, with its deficiency linked to amygdala shrinkage and impaired social incentive evaluation. A study published in Molecular Psychiatry has linked changes in brain [...]
How much permafrost will melt this century, and where will its carbon go?
Among the many things global warming will be melting this century—sea ice, land glaciers and tourist businesses in seaside towns across the world—is permafrost. Lying underneath 15% of the northern hemisphere, permafrost consists of [...]
A Physics Discovery So Strange It’s Changing Quantum Theory
MIT physicists surprised to discover electrons in pentalayer graphene can exhibit fractional charge. New theoretical research from MIT physicists explains how it could work, suggesting that electron interactions in confined two-dimensional spaces lead to novel quantum states, [...]
Inside the Nano-Universe: New 3D X-Ray Imaging Transforms Material Science
A cutting-edge X-ray method reveals the 3D orientation of nanoscale material structures, offering fresh insights into their functionality. Researchers at the Swiss Light Source (SLS) have developed a groundbreaking technique called X-ray linear dichroic orientation tomography [...]
X-chromosome study reveals hidden genetic links to Alzheimer’s disease
Despite decades of research, the X-chromosome’s impact on Alzheimer’s was largely ignored until now. Explore how seven newly discovered genetic loci could revolutionize our understanding of the disease. Conventional investigations of the genetic contributors [...]
The Unresolved Puzzle of Long COVID: 30% of Young People Still Suffer After Two Years
A UCL study found that 70% of young people with long Covid recovered within 24 months, but recovery was less likely among older teenagers, females, and those from deprived backgrounds. Researchers emphasized the need [...]
Needle-Free: New Nano-Vaccine Effective Against All COVID-19 Variants
A new nano-vaccine developed by TAU and the University of Lisbon offers a needle-free, room-temperature-storable solution against COVID-19, targeting all key variants effectively. Professor Ronit Satchi-Fainaro’s lab at Tel Aviv University’s Faculty of Medical and [...]
Photoacoustic PDA-ICG Nanoprobe for Detecting Senescent Cells in Cancer
A study in Scientific Reports evaluated a photoacoustic polydopamine-indocyanine green (PDA-ICG) nanoprobe for detecting senescent cells. Senescent cells play a role in tumor progression and therapeutic resistance, with potential adverse effects such as inflammation and tissue [...]
How Dysregulated Cell Signaling Causes Disease
Cell signaling is crucial for cells to communicate and function correctly. Disruptions in these pathways, caused by genetic mutations or environmental factors, can lead to uncontrolled cell growth, improper immune responses, or errors in [...]
Scientists Develop Super-Strong, Eco-Friendly Plastic That Bacteria Can Eat
Researchers at the Weizmann Institute have developed a biodegradable composite material that could play a significant role in addressing the global plastic waste crisis. Billions of tons of plastic waste clutter our planet. Most [...]
Building a “Google Maps” for Biology: Human Cell Atlas Revolutionizes Medicine
New research from the Human Cell Atlas offers insights into cell development, disease mechanisms, and genetic influences, enhancing our understanding of human biology and health. The Human Cell Atlas (HCA) consortium has made significant [...]
Bioeconomic Potential: Scientists Just Found 140 Reasons to Love Spider Venom
Researchers at the LOEWE Centre for Translational Biodiversity Genomics (TBG) have discovered a significant diversity of enzymes in spider venom, previously overshadowed by the focus on neurotoxins. These enzymes, found across 140 different families, [...]
