Changes in neuroplasticity and neuronal adaptative mechanisms have been postulated as origin and/or main pathophysiological factor in neurodegenerative diseases. To analyze these theories, a comparative morphohistochemical study on the cerebral (prefrontal) and cerebellar (neocerebellar) cortex from Alzheimer's (AD) and Creutzfeldt-Jakob (CJD) post-mortem brains has been carried out. Variations in putative markers of neuroplasticity and neuronal adaptation (synaptic proteins such as drebrin and SNAP-25; nuclear factor NF kappa Beta -NFkB-; neuronal isoform of oxide nitric synthase -nNOS) have been studied in close association with neuropathological markers (beta-protein deposition - amyloid in AD and PrPsc in CJD-; microglial activation, induction of iNOS and cyclooxygenase 2 -COX-2). Results have shown sharp variations in these markers when compared AD and CJD; cerebral and cerebellar cortex; different areas of these anatomical regions; and different sets of neurons and glial cells. The meaining of somme of these markers (NFkB; nNOS; synaptic proteins) could be variable (plastic/adaptative or involutive), depending on different factors (disease, anatomical region, general or local factors, etc.). Neuroplasticity is evident in several brain regions or neurons, but this neuronal feature decreases in different form depending also on the disease and the anatomical region. Their relationships to the neuropathological findings were also variable. In conclusion, the activation of these putative markers of neuroplasticity, considering as therapeutical targets, in advanced steps of the diseases, could activate neuronal involutive phenomena in several regions or neurons.