Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus
| Autor: | Ossi Nerg, Lakshman Puli, Henrik Zetterberg, Hilkka Soininen, Jouni Ihalainen, Mikael von und zu Fraunberg, Okko T. Pyykkö, Heikki Tanila, Anne M. Koivisto, Mikko Hiltunen, Ville Leinonen, Juha E. Jääskeläinen, Irina Alafuzoff, Toni T. Seppälä, Seppo Helisalmi, Jaana Rummukainen, Jaakko Rinne, Sanna-Kaisa Herukka |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Microdialysis Amyloid beta Apolipoprotein E4 tau Proteins Cerebrospinal fluid Normal pressure hydrocephalus Interstitial fluid Biopsy Medicine Humans Aged Aged 80 and over Amyloid beta-Peptides Chi-Square Distribution medicine.diagnostic_test biology business.industry General Neuroscience Brain biopsy Brain Extracellular Fluid General Medicine Human brain Middle Aged medicine.disease Hydrocephalus Normal Pressure Peptide Fragments Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure biology.protein Female Geriatrics and Gerontology business Cognition Disorders |
| Zdroj: | Journal of Alzheimer's disease : JAD. 46(1) |
| ISSN: | 1875-8908 |
| Popis: | Background: Amyloid-beta (A beta(1-42)), total tau (T-tau), and phosphorylated tau (P-tau(181)) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble A beta decreases with increasing age and advanced A beta pathology as seen similarly in CSF. Objective: To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). Methods: Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. Results: ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. A beta(1-42) and P-tau(181) remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while A beta(1-42) levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau(181) (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF A beta(1-42) levels than those six without amyloid pathology. Conclusions: This is the first study to report ISF A beta and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease. |
| Databáze: | OpenAIRE |
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