The use of proteomics in biomarker discovery in neurodegenerative diseases.
Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein, beta-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of both beta-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-beta-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases.
Davidsson
Pia
P
Discovery Medicine/Molecular Sciences, AstraZeneca R&D, Mölndal, Sweden. pia.davidsson@astrazeneca.com
Sjögren
Magnus
M
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis; D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D001057:Apolipoproteins E / Q000032:analysis; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007122:Immunoelectrophoresis; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D040901:Proteomics; D013569:Synapses / Q000737:chemistry; D016875:tau Proteins / Q000032:analysis
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D016875:tau Proteins