ABSTRACT
The pathological hallmarks of Alzheimer's disease are aggregation and accumulation of amyloid-ß and tau proteins. So far most interventional studies have focused on the removal of the toxic protein products, such as antibody-based immunotherapies targeted against amyloid-ß and tau proteins; however, the development of gene therapies targeting gene products involved in the disease has opened up new therapeutic strategies to reduce the development of toxic protein aggregates by inhibiting the translation of pathological Alzheimer genes using antisense oligonucleotides (ASO). This has a timely influence on development of the disease. This article gives an overview of new advances in ASO-based treatment strategies for Alzheimer's disease.
Subject(s)
Alzheimer Disease , Genetic Therapy , Alzheimer Disease/therapy , Amyloid beta-Peptides/genetics , Genetic Therapy/trends , Humans , Immunotherapy/trends , Oligonucleotides, Antisense/therapeutic use , tau Proteins/metabolismABSTRACT
OBJECTIVES: S100B was proposed to be a CSF and blood biomarker in a number of neurological diseases. The route of S100B to the CSF and the blood in neurodegenerative diseases is unclear. To assess the impact of the physiological or impaired blood-CSF-barrier (BCSFB) function on S100B concentrations in CSF and serum, we analysed S100B in correlation of the albumin quotient. MATERIALS AND METHODS: S100Bserum and S100BCSF were quantified in samples from patients with a variety of neurological diseases using an immunoluminometric assay (Sangtec LIA-mat). Measures were analysed for a potential relation to the CSF/serum-albumin quotient (Qalb ), which indicates the BCSFB functionality. RESULTS: We reasserted increased S100B concentrations in CSF and serum of CJD patients. Elevated S100Bserum correlated with elevated S100BCSF in all diagnoses but with exceptions. Neither S100BCSF nor S100Bserum did correlate with Qalb , even when the BCSFB function was progressively impaired as demonstrated by increased Qalb . CONCLUSIONS: The lack of correlation between Qalb and S100BCSF is typically seen for proteins which are brain derived. Therefore, we propose that S100B enters the blood with the bulk flow via Pacchioni's granules and along the spinal nerve sheaths.
