Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus
| Autor: | Tuomas Rauramaa, Darrel J. Pemberton, Maarten Timmers, Mikko Hiltunen, Hartmuth C. Kolb, Antti Junkkari, Peter van der Ark, Heikki Lukkarinen, Ville E. Korhonen, Johannes Streffer, Ville Leinonen, Sebastiaan Engelborghs, Anne M Koivisto, Henrik Zetterberg, Sanna-Kaisa Herukka, Luc Janssens, Ina Tesseur, Astrid Bottelbergs, Kaj Blennow, Luc Van Nueten, Randy Slemmon |
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| Přispěvatelé: | Department of Neurosciences, University of Helsinki, Geriatrian yksikkö, Helsinki University Hospital Area, Clinical sciences, Neuroprotection & Neuromodulation, Neurology |
| Rok vydání: | 2021 |
| Předmět: |
Male
Apolipoprotein E Gastroenterology INCREASE 3124 Neurology and psychiatry 0302 clinical medicine Cerebrospinal fluid Neurofilament Proteins PHOSPHORYLATED TAU neurofilament light Medicine Neurogranin Phosphorylation Aged 80 and over 0303 health sciences neurogranin biology medicine.diagnostic_test Aβ42 General Neuroscience Neurodegeneration P-tau General Medicine Middle Aged AMYLOID-BETA Cerebrospinal Fluid Shunts Hydrocephalus Normal Pressure ALZHEIMERS-DISEASE Psychiatry and Mental health Clinical Psychology Regression Analysis Biomarker (medicine) Female idiopathic normal pressure hydrocephalus Research Article medicine.medical_specialty Amyloid beta CSF BIOMARKERS tau Proteins DIAGNOSIS Risk Assessment 03 medical and health sciences Lumbar Alzheimer Disease Internal medicine Humans PROTEIN NEUROGRANIN Aged 030304 developmental biology Amyloid beta-Peptides T-tau business.industry neurology Brain biopsy 3112 Neurosciences A beta(42) biomarkers SYNAPTIC PROTEIN medicine.disease Peptide Fragments biology.protein Human medicine Geriatrics and Gerontology CORTICAL BRAIN BIOPSY business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's disease Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. Objective: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-beta (A beta) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. Methods: L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed A beta plaques in frontal cortical brain biopsy and 13 iNPH patients without A beta pathology. CSF Amyloid-beta(42) (A beta(42)), total tau (T-tau), phosphorylated tau (P-tau(181)), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. Results: All biomarkers but A beta(42) increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. A beta(42) instead showed divergent longitudinal decrease between A beta-positive and -negative patients in L-CSF, and thereafter increase in A beta-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (A beta(42) R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (A beta(42) 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only A beta(42) showed higher concentration in non-carriers of allele epsilon 4. Conclusion: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy A beta pathology, while NFL normalized toward its pre-shunt levels. A beta(42) as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V-than L-CSF yet showing strong correlations. |
| Databáze: | OpenAIRE |
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