**2.4 Skin**

276 Biomarker

overcome many of the problems with reduced sensitivity and specificity. For example, the development of whole genome amplification (WGA) protocols allow researchers to perform reliable genome-wide scans using archived residual blood samples from newborn screening programs, which are standard practice in several countries (Hollegaard et al., 2009). Several studies have shown that despite being considered too vulnerable to degradation by ribonucleases, RNA could be recovered from DBS samples that had been stored for 15-20 years, and be successfully amplified by reverse transcription-PCR (Karlsson et al., 2003; Zubakov et al., 2008). Also, dried blood spots recently become the sample type of choice for HIV screening in low-resource settings (Sherman et al., 2005; Uttayamakul et al., 2005).

Cerebrospinal fluid (CSF) is a cell-free, colorless liquid that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord. It is usually obtained through lumbar puncture. CSF has been rediscovered in the post-genomic era, as a great source of potential protein biomarkers for various diseases as it bathes the brain and other neurological tissues. Analysis of CSF allows rapid screening, low sample consumption, and accurate protein identification by proteomic technology (Guerreiro et al., 2006; Zheng et al., 2003). Brain proteins in CSF are also important for diagnosis of noninflammatory CNS diseases. Examples of conditions in which these proteins are diagnostically relevant include degenerative diseases (Otto et al., 1997; Ranganathan et al., 2005), tumors (Zheng et al., 2003), hypoxias and brain infarction (Schaarschmidt et al., 1994). Advancements in nucleic acid (NA) amplification techniques have transformed the diagnosis of bacterial and viral infections of the central nervous system. Because of their enhanced sensitivity, these methods enable detection of very low amounts of pathogenic genomes in cerebrospinal fluid. Diagnosis of several viral CNS infections, such as herpes encephalitis, enterovirus meningitis and other viral infections occurring in human immunodeficiency virus-infected persons are currently performed using cerebrospinal fluid (Cinque, Bossolasco, & Lundkvist, 2003). MicroRNAs are also becoming an important analyte in CSF for the identification of neurological disease (Baraniskin et al., 2011; Cogswell et al., 2008; De Smaele et al., 2010). For example, miRNAs isolated from the frozen cerebrospinal fluid of Alzheimer disease-affected (AD) and non-affected patients showed distinctly different expression profiles (Cogswell et al., 2008). Notably miRNAs linked to immune cell functions including innate immunity and T cell activation and differentiation

Combining mRNA studies with protein expression analysis may provide a more global picture of the biological processes associated with CNS disorders. Information gathered could lead to the development of select biological indices (biomarkers) for guiding CNS

Saliva is an easily obtainable tissue that has been used in forensics for decades (Sweet et al., 1997). However, new molecular profiling kits for voluntary saliva collection have made saliva an increasingly useful clinical biomarker tissue. The collection process is noninvasive, and can even be collected at home or in isolated locations using some of the newer

**2.2 Cerebrospinal fluid** 

were up-regulated in AD.

diagnosis and therapy.

**2.3 Saliva** 
