Reelin is an extracellular
glycoprotein that modulates neuronal function and synaptic plasticity in the adult brain. Decreased levels of Reelin activity have been postulated as a key factor during neurodegeneration in Alzheimer´s disease (AD) and in aging. Thus, changes in levels of full-length Reelin and Reelin fragments have been revealed in cerebrospinal fluid (CSF) and in post-mortem brains samples of AD patients with respect to non-AD patients. However, conflicting studies have reported decreased or unchanged levels of full-length Reelin in AD patients compared to control (nND) cases in post-mortem brains and CSF samples. In addition, a compelling analysis of Reelin levels in
neurodegenerative diseases other than AD is missing. In this study, we analyzed brain levels of RELN
mRNA and
Reelin protein in post-mortem frontal cortex samples from different sporadic AD stages,
Parkinson's disease with
dementia (PDD), and
Creutzfeldt-Jakob disease (sCJD), obtained from five different Biobanks. In addition, we measured
Reelin protein levels in CSF samples of patients with
mild cognitive impairment (MCI),
dementia, or sCJD diagnosis and a group of neurologically healthy cases. The results indicate an increase in RELN
mRNA in the frontal cortex of advanced stages of AD and in sCJD(I) compared to controls. This was not observed in PDD and early AD stages. However,
Reelin protein levels in frontal cortex samples were unchanged between nND and advanced AD stages and PDD. Nevertheless, they decreased in the CSF of patients with
dementia in comparison to those not suffering with
dementia and patients with MCI. With respect to sCJD, there was a tendency to increase in brain samples in comparison to nND and to decrease in the CSF with respect to nND. In conclusion, Reelin levels in CSF cannot be considered as a diagnostic
biomarker for AD or PDD. However, we feel that the CSF Reelin changes observed between MCI, patients with
dementia, and sCJD might be helpful in generating a
biomarker signature in prodromal studies of unidentified
dementia and sCJD.