Factors related to blood-based biomarkers for neurodegenerative diseases and their intergenerational associations in the Young Finns Study: a cohort study.

BACKGROUND

Blood-based biomarkers (BBM) of neurodegenerative diseases are emerging as cost-effective tools in the differential diagnostics of Alzheimer's disease and other dementias. Scarce data exist about factors explaining BBM variation in population-based cohorts, and their intergenerational associations are unknown. This study aimed to characterise BBM distributions among a population-based cohort, investigate the association of a wide array of factors with BBM both in midlife and old age, and investigate intergenerational associations of BBM.

METHODS

We measured BBM detecting amyloid β and tau pathologies, including amyloid β42, amyloid β40, and phosphorylated Tau (pTau)-217, as well as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in the multigenerational Young Finns Study participants (n=1237, age 41-56 years) and their parents (n=814, age 59-90 years) using the Quanterix Simoa HD-X analyser. Standard statistical methods were used to examine the associations between BBM and age, sex, genetic factors, a plethora of cardiometabolic markers, liver and kidney function, and lifestyle factors, as well as their intergenerational associations.

FINDINGS

Increased age was associated with adverse BBM concentrations. Of the various investigated factors, the most robust associations towards adverse BBM concentration were found for APOE ε4 carrier status among parents (amyloid β42:40 ratio, pTau-217, and GFAP) and high serum creatinine concentration in both generations (pTau-217, GFAP, and NfL). Several factors related to glucose metabolism and dyslipidaemia were negatively associated with all BBM, but adjusting for BMI diluted many of these associations. Statistically significant intergenerational correlations ranged from 0·20 to 0·33 and were mostly observed between mothers and offspring in pTau-217, GFAP, and NfL. No intergenerational correlations existed in amyloid β42:40 ratio.

INTERPRETATION

We identified several factors that might influence BBM concentrations, parental transmission being one of them. For reliable use of BBM in clinical practice, it is important to identify which factors directly link to amyloid β and tau pathology and which factors influence BBM concentrations due to other physiological processes.

FUNDING

Research Council of Finland, Social Insurance Institution of Finland, Competitive State Research Financing of the Expert Responsibility area of the Kuopio, Tampere and Turku University Hospitals, Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation for Cardiovascular Research, Finnish Cultural Foundation, The Sigrid Juselius Foundation, Tampere Tuberculosis Foundation, Emil Aaltonen Foundation, Yrjö Jahnsson Foundation, Signe and Ane Gyllenberg Foundation, Jenny and Antti Wihuri Foundation, Diabetes Research Foundation of the Finnish Diabetes Association, EU Horizon 2020, European Research Council, Tampere University Hospital Supporting Foundation, Finnish Society of Clinical Chemistry, the Jane and Aatos Erkko Foundation, and the Finnish Brain Foundation.