Early Blood Biological Markers Identified to Predict Diseases

Doctors are increasingly turning to blood biomarkers to detect diseases before symptoms emerge. Identifying these markers can lead to faster diagnoses and more effective treatments, improving outcomes for conditions like cancer, cardiovascular disease, and neurodegenerative disorders.

Researchers have pinpointed biological molecules in the blood that may serve as early warning signs. Understanding their function and predictive potential is crucial for advancing diagnostic medicine.

Key Blood Proteins

Certain blood proteins offer insights into physiological changes that precede symptoms. Among these, albumin, globulins, and fibrinogen have been extensively studied. Albumin, the most abundant plasma protein, helps maintain oncotic pressure and transport substances. Low albumin levels have been linked to early-stage liver disease and malnutrition, while high levels may indicate dehydration. Reduced albumin can also signal declining kidney function before symptoms appear.

Fibrinogen, a glycoprotein involved in clot formation, has been identified as an early marker for cardiovascular disease. Elevated fibrinogen levels correlate with a higher risk of thrombosis, even in asymptomatic individuals. A study in The Lancet found that those with fibrinogen levels in the upper quartile had a significantly greater likelihood of developing coronary artery disease within five years. Monitoring fibrinogen concentrations could help identify at-risk individuals early, enabling lifestyle changes or medical intervention.

Transthyretin, a transporter of thyroid hormones and retinol-binding protein, has been associated with early malnutrition and neurodegenerative disorders like Alzheimer’s disease. A JAMA Neurology meta-analysis found lower transthyretin levels in patients with mild cognitive impairment, suggesting its potential as a preclinical biomarker. Given its role in amyloid-beta clearance, researchers are exploring whether transthyretin alterations precede pathological brain changes, making it a candidate for early detection strategies.

Enzymes And Metabolites

Biochemical changes in the bloodstream often occur before clinical disease onset, making enzymes and metabolites valuable early indicators. Enzymes regulate metabolic pathways, and fluctuations in their activity can reflect underlying pathology. Gamma-glutamyl transferase (GGT), involved in glutathione metabolism, has been linked to oxidative stress and early liver dysfunction. A longitudinal study in Hepatology found that elevated GGT levels predicted non-alcoholic fatty liver disease (NAFLD) progression years before imaging detected hepatic fibrosis. Since NAFLD can lead to cirrhosis and liver cancer, routine GGT monitoring could facilitate earlier intervention.

Creatine kinase (CK), particularly its MB isoform (CK-MB), serves as an early marker for muscular and cardiovascular conditions. Traditionally used to diagnose acute coronary syndromes, recent studies suggest that subclinical CK-MB elevations may indicate early myocardial stress. A Circulation study found that individuals with persistently elevated CK-MB levels were more likely to develop heart failure within a decade, even without prior cardiac events. This highlights the potential of enzyme-based surveillance in identifying at-risk individuals before irreversible heart damage occurs.

Metabolites also provide insight into disease development. Elevated homocysteine levels have been associated with early-stage cardiovascular and neurovascular diseases. A meta-analysis in The American Journal of Clinical Nutrition found that individuals with high homocysteine levels had an increased risk of stroke and cognitive decline. Similarly, branched-chain amino acids (BCAAs), involved in protein metabolism, have been linked to early insulin resistance. Research in Diabetes Care found that elevated BCAA levels were detectable years before type 2 diabetes onset, reinforcing their potential as metabolic warning signals.

Inflammatory Indicators

Chronic inflammation often precedes diseases such as cardiovascular conditions, neurodegenerative disorders, and metabolic syndromes. Inflammatory biomarkers provide insight into early disease stages. C-reactive protein (CRP), synthesized by the liver in response to systemic inflammation, has strong predictive value. Research in The New England Journal of Medicine found that individuals with high-sensitivity CRP (hs-CRP) levels above 2 mg/L had nearly double the risk of coronary artery disease, even when accounting for cholesterol and blood pressure.

Interleukin-6 (IL-6) has also emerged as a key early marker, particularly in age-related diseases. A longitudinal study in JAMA Internal Medicine found that elevated IL-6 levels in midlife were associated with a significantly increased likelihood of cognitive decline over the following two decades. Tracking IL-6 concentrations could enable earlier interventions to mitigate long-term neurological damage.

Fibrinogen, beyond its role in clot formation, has been linked to systemic inflammation and endothelial dysfunction. Studies suggest that individuals with persistently high fibrinogen levels face a greater risk of thrombotic events, even without traditional cardiovascular risk factors. This has led to growing interest in fibrinogen testing for individuals at risk of stroke or peripheral artery disease.

Potential Genetic Links

Genetic predisposition influences disease susceptibility, and researchers are identifying blood biomarkers that reflect inherited risk. Advances in genomic sequencing have revealed gene variants associated with altered protein expression, offering insight into early disease processes. The APOE ε4 allele, for example, is linked to an increased risk of Alzheimer’s disease. Carriers of this variant often exhibit altered lipid transport proteins in their blood decades before cognitive decline, suggesting a molecular signature that could help identify at-risk populations for early intervention.

Genetic variations affecting metabolic pathways also contribute to disease risk. Mutations in the PCSK9 gene influence cholesterol regulation by modifying low-density lipoprotein (LDL) receptor function. Gain-of-function mutations in PCSK9 lead to elevated LDL cholesterol levels, increasing cardiovascular risk even in the absence of lifestyle factors. Conversely, loss-of-function mutations result in lower cholesterol levels and reduced heart disease incidence, inspiring the development of PCSK9 inhibitors as a therapeutic approach.

Marker Panel Comparisons

While individual biomarkers provide valuable insights, integrating multiple markers into diagnostic panels enhances predictive accuracy. Single biomarkers often lack the specificity or sensitivity needed for reliable early detection. By combining multiple indicators, physicians can assess disease risk with greater precision, reducing false positives and missed diagnoses. Advances in machine learning and bioinformatics have further refined biomarker analysis, enabling more personalized disease risk assessments.

For example, cardiovascular risk assessment has expanded beyond traditional lipid measurements to include panels incorporating high-sensitivity CRP, fibrinogen, and lipoprotein-associated phospholipase A2 (Lp-PLA2). Studies show that individuals with elevated levels of all three biomarkers face a significantly higher risk of atherosclerosis than those with only one abnormal marker. Similarly, neurodegenerative disease panels now integrate plasma neurofilament light chain (NfL) with tau protein and amyloid-beta ratios, improving early-stage Alzheimer’s detection. As research advances, these multi-marker approaches may become standard in preventive medicine, enabling physicians to identify at-risk patients before irreversible damage occurs.