Cerebrospinal fluid levels of a 20-22 kDa NH2 fragment of human tau provide a novel neuronal injury biomarker in Alzheimer's disease and other dementias.
Truncation at N-terminal domain of tau protein is early associated with neurofibrillary pathology in several human tauopathies, including Alzheimer's disease (AD). In affected subjects, the monitoring of total (t-tau) and/or phosphorylated tau (p-tau) levels in cerebrospinal fluid (CSF) provides a reliable, indirect evaluation of cellular changes occurring in vivo and the identification of additional CSF biomarkers would better assist with the clinical practice, allowing a broader profile of underlying ongoing neurodegeneration. Here we show that a 20-22 kDa NH2-truncated form of human tau (i.e., NH2htau), a neurotoxic fragment of the full length protein (htau40) that we previously found in synapses from subjects affected by different tauopathies: (i) is not a normal constituent of CSF, unlike t-tau and p-tau, being exceptionally detected in patients without cognitive impairment; (ii) discriminates, with a weak specificity of 65% but a high sensitivity of 85%, patients carrying a large spectrum of neurodegenerative diseases associated with cognitive deterioration (i.e., AD, frontotemporal lobar degeneration, Parkinson's disease with dementia, vascular dementia, mixed dementia, etc.) from subjects affected by other neurological disorders without mnesic disability; and (iii) is a neuronal injury biomarker as its levels in CSF are not related to the severity and progression of cognitive decline. The dynamic evaluation of NH2htau in CSF might add some useful hints in the ordinary clinical practice as it provides a novel, general biomarker for human tauopathies and other neurodegenerative diseases associated with dementia.
Institute of Translational Pharmacology (IFT)-CNR, Rome, Italy European Brain Research Institute (EBRI), Rome, Italy.
Giuseppina
G
Amadoro
Institute of Translational Pharmacology (IFT)-CNR, Rome, Italy.
Veronica
V
Corsetti
Department of Experimental Medicine and Surgery, Tor Vergata General Hospital, The University of Rome Tor Vergata, Rome, Italy.
Giulia Maria
GM
Sancesario
Department of Systems Medicine, Tor Vergata General Hospital, The University of Rome Tor Vergata, Rome, Italy.
Adele
A
Lubrano
Department of Systems Medicine, Tor Vergata General Hospital, The University of Rome Tor Vergata, Rome, Italy.
Gaia
G
Melchiorri
Department of Experimental Medicine and Surgery, Tor Vergata General Hospital, The University of Rome Tor Vergata, Rome, Italy.
Sergio
S
Bernardini
European Brain Research Institute (EBRI), Rome, Italy.
Pietro
P
Calissano
Department of Systems Medicine, Tor Vergata General Hospital, The University of Rome Tor Vergata, Rome, Italy.
Giuseppe
G
Sancesario
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015331:Cohort Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
Alzheimer's disease; biomarker; cerebrospinal fluid; tau truncation; tauopathies