NEW research has shown that age, APOE ε4 carrier status, and kidney function are strongly associated with blood-based biomarkers (BBM) of neurodegenerative disease, highlighting the importance of considering hereditary and metabolic factors in biomarker interpretation.
Blood-based biomarkers are increasingly recognised as valuable and cost-effective tools for the early detection and diagnosis of neurodegenerative conditions such as Alzheimer’s disease and related dementias. Despite their growing clinical relevance, there is limited knowledge regarding population-wide determinants of these biomarkers, the influence of various physiological and genetic factors, and the degree to which they might be inherited across generations. Gaining a clearer understanding is essential for their reliable clinical application and accurate interpretation in both research and patient care.
The Young Finns Study investigated the distribution and determinants of key BBMs—amyloid β42, amyloid β40, phosphorylated tau (pTau)-217, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL)—in 1,237 adults aged 41–56 years and 814 of their parents aged 59–90 years. Biomarkers were measured using the Quanterix Simoa HD-X analyser. Statistical associations were assessed with respect to age, sex, genetics (notably APOE ε4 status), cardiometabolic markers, kidney and liver function, and lifestyle factors. Age was associated with a typical increase in adverse BBM levels. The most consistent associations were seen for parental APOE ε4 carrier status, particularly with the amyloid β42:40 ratio, pTau-217, and GFAP, and for elevated serum creatinine—which reflects reduced kidney function—across both generations (notably affecting pTau-217, GFAP, and NfL values). While some factors related to glucose metabolism and dyslipidaemia were inversely associated with BBMs, these effects were often attenuated when adjusting for body mass index. Statistically significant correlations between parents and offspring, especially for pTau-217, GFAP, and NfL, were modest (0.20 to 0.33) and stronger between mothers and their children. Intergenerational association was not seen for amyloid β42:40 ratio.
These findings underline the complex interplay of genetic, renal, and metabolic factors on neurological biomarker concentrations and the need for careful interpretation in clinical practice. Understanding the biological and hereditary factors influencing BBM values will help clinicians distinguish changes related to true neurodegenerative pathology from those reflecting other physiological or familial influences.
Reference
Heiskanen MA et al. Factors related to blood-based biomarkers for neurodegenerative diseases and their intergenerational associations in the Young Finns Study: a cohort study. The Lancet Healthy Longevity. 2025;6(6).
