Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients

Abstract

Background Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Methods Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Results Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1). Conclusions pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.

The pathophysiology of cognitive impairment in individuals with heart failure: a systematic review

“…The second study reported increased cerebral and hippocampal atrophy scores. It also illustrated increased WMH, phosphorylated Tau protein (pTau) and neurofilament light chain (NfL), which are key biomarkers of AD ( 41 ). These two studies focused on chronic HF, with more participants having ischemic etiology.…”

A Set of Possible Markers for Monitoring Heart Failure and Cognitive Impairment Associated: A Review of Literature from the Past 5 Years

“…Other authors have found that NfL is elevated in individuals with heart disease [42]. Traub et al [43] measured serum levels of pTau and NfL in patients with HF, noting that they are affected by age-dependent renal and cardiac dysfunction.…”

Neurodegeneration is strongly linked to heart failure severity and outcomes: framing the cardiocerebral syndrome

“…A recent trial in HF patients found that elevated NfL levels were related both to white matter hyperintensities as well as hippocampal atrophy 49 . The former is a sign of chronic microvascular damage while the latter is closely related to AD pathology, suggesting that the elevation could be explained by an interplay of cardiovascular changes and amyloid beta-driven pathology.…”