Amyloid-β and tau dynamics in human brain interstitial fluid in patients with suspected normal pressure hydrocephalus

Sanna-Kaisa Herukka, Jaana Rummukainen, Jouni Ihalainen, Mikael von und zu Fraunberg, Anne M. Koivisto, Ossi Nerg, Lakshman K. Puli, Toni T. Seppälä, Henrik Zetterberg, Okko T. Pyykkö, Seppo Helisalmi, Heikki Tanila, Irina Alafuzoff, Mikko Hiltunen, Jaakko Rinne, Hilkka Soininen, Juha E. Jääskeläinen, Ville Leinonen

Research output: Contribution to journalArticleScientificpeer-review

36 Citations (Scopus)

Abstract

Background: Amyloid-′ (A′1-42), total tau (T-tau), and phosphorylated tau (P-tau181) 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′ decreases with increasing age and advanced A′ 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′1-42 and P-tau181 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′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-tau181 (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF A′1-42 levels than those six without amyloid pathology. Conclusions: This is the first study to report ISF A′ 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.

Original languageEnglish
Pages (from-to)261-269
Number of pages9
JournalJournal of Alzheimer's Disease
Volume46
Issue number1
DOIs
Publication statusPublished - 7 May 2015
Externally publishedYes
Publication typeA1 Journal article-refereed

Keywords

  • Alzheimer's disease
  • amyloid-′
  • biomarkers
  • normal pressure hydrocephalus
  • tau

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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