A window into the heterogeneity of human cerebrospinal fluid Aβ peptides

Abstract

The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (Aβ) peptides leading to the formation of neurotoxic brain Aβ assemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF Aβ peptides. Specifically, we focused our attention on the heterogeneity of the CSF Aβ world discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating Aβ assemblies, and (3) communication modes for Aβ peptides and their microenvironment targets. Finally, we suggest that Aβ peptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function.

Figure 1

Schematic representation of the ‘‘Push and Pull Control” of structural and functional plasticity of neuronal circuits and how this control is related to learning processes (plastic changes of the circuits) and maintenance of the memory traces (stability of the circuits). The possible actions of Aβ peptides as double-edged sword signals are indicated. Broken arrows indicate reduction or inhibition.