TY  - JOUR
A1  - Traub, Jan
A1  - Otto, Markus
A1  - Sell, Roxane
A1  - Göpfert, Dennis
A1  - Homola, György
A1  - Steinacker, Petra
A1  - Oeckl, Patrick
A1  - Morbach, Caroline
A1  - Frantz, Stefan
A1  - Pham, Mirko
A1  - Störk, Stefan
A1  - Stoll, Guido
A1  - Frey, Anna
T1  - Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients
JF  - Alzheimer's Research & Therapy
N2  - 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.
KW  - Alzheimer’s dementia
KW  - heart failure
KW  - cognitive impairment
KW  - neurofilament light chain
KW  - phosphorylated tau protein
KW  - renal function
KW  - age
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300515
VL  - 14
ER  -