Mechanical Dilution of Beta-amyloid Peptide and Phosphorylated Tau Protein in Alzheimer's Disease: Too Simple to be True?

Manuel Menéndez González

doi:10.7759/cureus.1062

Abstract

The neuropathology of Alzheimer's disease (AD) is characterized by the widespread accumulation of neuritic plaques and neurofibrillary tangles composed of deposits of beta-amyloid peptide (Aβ) and abnormally phosphorylated tau protein (phospho-tau) respectively. Considerable effort has been expended to identify methods to retard the deposition of these proteins or to enhance their clearance. It is strikingly surprising that until now, very few researchers have attempted to remove these proteins using mechanical procedures.In this article, we start by showing the rationale of mechanical dilution of cerebrospinal fluid (CSF) as a therapeutic approach in AD. Then, we present models of implantable systems allowing mechanical dilution of CSF by means of CSF replacement and CSF filtration (liquorpheresis). We conclude that even though this approach seems simplistic, it is feasible and deserves exploration.

Highlights

Rationale for mechanical dilution of cerebrospinal fluid (CSF) in Alzheimer's disease (AD)The neuropathology of AD is characterized by the widespread accumulation of neuritic plaques and neurofibrillary tangles composed of deposits of beta-amyloid peptide (Aβ) and abnormally phosphorylated tau protein respectively (Figure 1)
Soluble Aβ can be removed from the brain by various clearance systems including enzymatic degradation and cellular uptake, transport across the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), interstitial fluid (ISF) bulk flow, and CSF absorption into the circulatory and lymphatic systems
We propose a new approach for mechanical clearance of Aβ and phospho-tau by diluting their concentration in the CSF continuously

Summary

Introduction

Rationale for mechanical dilution of cerebrospinal fluid (CSF) in Alzheimer's disease (AD). In one of these studies, authors found that high p-tau/Aβ1-42 ratios in ventricular CSF correlated with the presence of cortical AD pathology. If resistance to CSF outflow predominates, it results in NPH The authors of this theory have studied the safety and efficacy of improving CSF turnover in 29 patients (aged 62-85 years) with mild to moderate AD (NINDS-ADRDA criteria) by means of a novel, constant, and low-flow ventriculoperitoneal shunt (COGNIShunt, Redwood City, CA, USA). We propose a new approach for mechanical clearance of Aβ and phospho-tau by diluting their concentration in the CSF continuously. This can be achieved by using implantable systems for CSF replacement or CSF filtration. The concentration of Aβ and tau is much lower in the outflow fluid than in the inflow fluid

Discussion

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Disclosures