Abstract
BackgroundThe relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer’s disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients.MethodsMini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ42, Aβ40, Aβ38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1).ResultsPreoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26.ConclusionsCSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.
Highlights
The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus has been inconclusive
Since CSF concentrations of total tau (T-tau), P-tau181, neurofilament light (NfL), Amyloid-β 38 (Aβ38), Amyloid-β 40 (Aβ40), Amyloid-β 42 (Aβ42), Soluble amyloid precursor protein α (sAPPα), Soluble amyloid precursor protein β (sAPPβ) and monocyte chemoattractant protein 1 (MCP1) were concordant in both cohorts, we pooled the cohorts for correlation analysis
Comparable results were seen between the postoperative Mini Mental State Examination (MMSE) values and biomarkers of T-tau (r = − 0.37, p < 0.0001, Fig. 2B), P-tau181 (r = − 0.30, p < 0.0001, Fig. 2D) and NfL (r = − 0.23, p = 0.006, Fig. 2F)
Summary
The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzhei‐ mer’s disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients. Idiopathic normal pressure hydrocephalus (iNPH) is characterized by a symptom triad of gait dysfunction, dementia and incontinence, accompanied by enlarged ventricles [1, 2]. The common symptom triad and shunt-surgery outcomes are usually. It has been suggested that poor shunt surgery outcomes are derived from commonly coexisting neurodegenerative diseases, such as Alzheimer’s disease (AD) or vascular degeneration [7, 8]. The association of a wider repertoire of AD biomarkers with postsurgery clinical features in iNPH are still somewhat inconclusive [10,11,12,13]
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