Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.

Reelin is a glycoprotein that is essential for the correct cytoarchitectonic organization of the developing CNS. Its function in the adult brain is less understood, although it has been proposed that Reelin is involved in signaling pathways linked to neurodegeneration. Here we analyzed Reelin expression in brains and cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and nondemented controls. We found a 40% increase in the Reelin protein levels in the cortex of AD patients compared with controls. Similar increases were detected at the Reelin mRNA transcriptional level. This expression correlates with parallel increases in CSF but not in plasma samples. Next, we examined whether CSF Reelin levels were also altered in neurological diseases, including frontotemporal dementia, progressive supranuclear palsy, and Parkinson's disease. The Reelin 180-kDa band increased in all of the neurodegenerative disorders analyzed. Moreover, the 180-kDa Reelin levels correlated positively with Tau protein in CSF. Finally, we studied the pattern of Reelin glycosylation by using several lectins and the anti-HNK-1 antibody. Glycosylation differed in plasma and CSF. Furthermore, the pattern of Reelin lectin binding differed between the CSF of controls and in AD. Our results show that Reelin is up-regulated in the brain and CSF in several neurodegenerative diseases and that CSF and plasma Reelin have distinct cellular origins, thereby supporting that Reelin is involved in the pathogenesis of a number of neurodegenerative diseases.eelin is an extracellular 420-kDa glycoprotein that binds to the transmembrane receptors apolipoprotein receptor 2 and very-low-density lipoprotein receptor (1, 2), which transduce the Reelin signal through the intracellular adapter disabled-1 (3-5). Reelin signaling triggers a disabled-1-dependent signaling cascade involving several kinases, which ultimately controls proper neuronal migration and positioning during CNS development (for review see ref. 6).The complex pattern of Reelin expression is consistent with evidence that this protein has multiple roles in brain development and adult brain function (7-9). In the adult mammalian brain, Reelin has been proposed to influence synaptogenesis and neural plasticity and to favor memory formation (8)(9)(10)(11)(12). Reelin is also expressed in peripheral tissues, including the liver, and is detected in blood (10, 13). However, whether brain and other tissues contribute to the pool of Reelin in blood remains to be elucidated. In this context, we recently reported the presence of detectable levels of Reelin in adult cerebrospinal fluid (CSF) (14).Furthermore, the involvement of the Reelin signaling pathway in neurodegeneration has also been proposed (1,6,9,(15)(16)(17). First, Reelin binds to apolipoprotein E (ApoE) receptors, and some ApoE gene polymorphisms are considered risk factors for Alzheimer's disease (AD). Moreover, the lack of Reelin is associated with increased phosphorylation of Tau (1, 2, 18), whose hyperphosphorylation leads to intracel...