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
Scientists Just Captured the Stunning Process That Shapes Chromosomes
Scientists at EMBL have captured how human chromosomes fold into their signature rod shape during cell division, using a groundbreaking method called LoopTrace. By observing overlapping DNA loops forming in high resolution, they revealed that large [...]
Bird Flu Virus Is Mutating Fast – Scientists Say Our Vaccines May Not Be Enough
H5N1 influenza is evolving rapidly, weakening the effectiveness of existing antibodies and increasing its potential threat to humans. Scientists at UNC Charlotte and MIT used high-performance computational modeling to analyze thousands of viral protein-antibody interactions, revealing [...]
Revolutionary Cancer Vaccine Targets All Solid Tumors
The method triggers immune responses that inhibit melanoma, triple-negative breast cancer, lung carcinoma, and ovarian cancer. Cancer treatment vaccines have been in development since 2010, when the first was approved for prostate cancer, followed [...]
Scientists Uncover Hidden Protein Driving Autoimmune Attacks
Scientists have uncovered a critical piece of the puzzle in autoimmune diseases: a protein that helps release immune response molecules. By studying an ultra-rare condition, researchers identified ArfGAP2 as a key player in immune [...]
Mediterranean neutrino observatory sets new limits on quantum gravity
Quantum gravity is the missing link between general relativity and quantum mechanics, the yet-to-be-discovered key to a unified theory capable of explaining both the infinitely large and the infinitely small. The solution to this [...]
Challenging Previous Beliefs: Japanese Scientists Discover Hidden Protector of Heart
A Japanese research team found that the oxidized form of glutathione (GSSG) may protect heart tissue by modifying a key protein, potentially offering a novel therapeutic approach for ischemic heart failure. A new study [...]
Millions May Have Long COVID – So Why Can’t They Get Diagnosed?
Millions of people in England may be living with Long Covid without even realizing it. A large-scale analysis found that nearly 10% suspect they might have the condition but remain uncertain, often due to [...]
Researchers Reveal What Happens to Your Brain When You Don’t Get Enough Sleep
What if poor sleep was doing more than just making you tired? Researchers have discovered that disrupted sleep in older adults interferes with the brain’s ability to clean out waste, leading to memory problems [...]
How to prevent chronic inflammation from zombie-like cells that accumulate with age
In humans and other multicellular organisms, cells multiply. This defining feature allows embryos to grow into adulthood, and enables the healing of the many bumps, bruises and scrapes along the way. Certain factors can [...]
Breakthrough for long Covid patients who lost sense of smell
A breakthrough nasal surgery has restored the sense of smell for a dozen long Covid patients. Experts at University College London Hospitals NHS Foundation Trust successfully employed a technique typically used for correcting blocked nasal passages, [...]
Scientists Invent Plastic That Can Dissolve In Seawater In Just A Few Hours
Plastic waste and pollution in the sea have been among the most serious environmental problems for decades, causing immense damage to marine life and ecosystems. However, a breakthrough discovery may offer a game-changing solution. [...]
Muscles from the 3D printer
Swiss researchers have developed a method for printing artificial muscles out of silicone. In the future, these could be used on both humans and robots. Swiss researchers have succeeded in printing artificial muscles out [...]
Beneficial genetic changes observed in regular blood donors
Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells. Understanding the differences in the mutations that accumulate [...]
Shocking Amounts of Microplastics in the Brain – It Could Be Increasing Our Risk of Dementia
The brain has higher concentrations of plastic particles compared to other organs, with increased levels found in dementia patients. In a comprehensive commentary published in Brain Medicine, researchers highlight alarming new evidence of microplastic accumulation [...]
Baffling Scientists for Centuries: New Study Unravels Mystery of Static Electricity
ISTA physicists demonstrate that contact electrification depends on the contact history of materials. For centuries, static electricity has intrigued and perplexed scientists. Now, researchers from the Waitukaitis group at the Institute of Science and [...]
Tumor “Stickiness” – Scientists Develop Potential New Way To Predict Cancer’s Spread
UC San Diego researchers have developed a device that predicts breast cancer aggressiveness by measuring tumor cell adhesion. Weakly adherent cells indicate a higher risk of metastasis, especially in early-stage DCIS. This innovation could [...]
