CSF biomarkers reflecting beta-amyloid and axonal pathology in Alzheimer's disease and related conditions
Year: 2011
Type: dissertation
Study design: Observational Study
Abstract: Cerebrospinal fluid (CSF) biomarkers may be used to identify and monitor pathological processes in the central nervous system. CSF biomarkers in Alzheimer’s disease (AD) include β-amyloid 42 (Aβ42), total-tau (T-tau) and phosphorylated-tau (P-tau), reflecting brain amyloid, axonal and tangle pathology, respectively. This dissertation aims at defining and validating CSF biomarkers for amyloid and axonal pathology in AD and related conditions.\nWe found that CSF Aβ42, T-tau and P-tau identified early-stage AD patients in a uniquely large multi-center study, and achieved very high diagnostic performance in a well-controlled mono-center study, with careful standardization of clinical procedures, sample handling, and laboratory performance. The distribution of CSF\nAβ42, T-tau and P-tau levels differed across age groups, likely reflecting agedependent\nprevalence of AD-like pathology in cognitively stable individuals. In the multi-center study, differences in the measured CSF biomarker levels were seen across laboratories. To monitor this, we established an external quality control\nprogram for CSF biomarkers. This program continues to grow and currently includes\nover 70 laboratories world-wide. BACE1 is a key enzyme for Aβ production, and therefore an attractive therapeutic target in AD. CSF biomarkers were studied to measure pharmacodynamic effects of BACE1-inhibitors. A panel of novel biomarkers was identified that may be used to track treatment effects in clinical trials. Finally, CSF biomarkers of amyloid and axonal pathology were studied in the\nlysosomal disease Niemann-Pick type C and in Lyme neuroborreliosis. Both these diseases had distinctly altered markers of amyloid metabolism and axonal pathology, and the biomarkers responded to treatments. In summary, this dissertation indicates that CSF biomarkers are useful in early AD diagnosis, identification of treatment effects and monitoring of amyloid and axonal pathology across neurological diseases. It introduces a quality control program to\nfacilitate global biomarker implementation. With the advancement of biomarkers as components of novel diagnostic criteria, knowledge of CSF biomarker alterations in different diseases will support optimal patient management.
Author: Niklas Mattsson
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1487724657