Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus.

Abstract

BACKGROUND:

Amyloid-β (Aβ1 - 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 Aβ decreases with increasing age and advanced Aβ 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. Aβ1 - 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 Aβ1 - 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 Aβ1 - 42 levels than those six without amyloid pathology.

CONCLUSIONS:

This is the first study to report ISF Aβ 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.

• Authors: 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
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 46 Issue 1 Pg. 261-9 ( 2015) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 25720406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Apolipoprotein E4
• Peptide Fragments
• amyloid beta-protein (1-42)
• tau Proteins

Topics

• Aged
• Aged, 80 and over
• Amyloid beta-Peptides (cerebrospinal fluid)
• Apolipoprotein E4 (genetics)
• Brain (metabolism, pathology)
• Chi-Square Distribution
• Cognition Disorders (etiology)
• Extracellular Fluid (metabolism)
• Female
• Humans
• Hydrocephalus, Normal Pressure (cerebrospinal fluid, complications, genetics, pathology)
• Male
• Microdialysis
• Middle Aged
• Peptide Fragments (cerebrospinal fluid)
• tau Proteins (cerebrospinal fluid)