Alpha-synuclein is not a requisite component of synaptic boutons in the adult human central nervous system

It is increasingly clear that the normal protein alpha -synuclein is in som e manner closely associated with presynaptic components of select neuronal types within the adult human central nervous system (CNS) and, in addition, that in its pathologically altered state alpha -synuclein aggregates selec tively in the form of filamentous inclusion bodies during certain progressi ve neurodegenerative disorders, such as familial and sporadic Parkinson's d isease. By having the antibody AFshp raised specifically to alpha -synuclei n to label Parkinson disease-specific Lewy bodies and Lewy neurites as well as synaptic boutons containing the unaltered protein, an initial attempt i s made to map the overall distribution pattern and describe the staining be havior of the immunoreactive punctae in select regions of the prosencephalo n. Neocortical immunolabeling is most prominent in the prodigious, but inco mpletely myelinated, association fields and faintest in the heavily myelina ted primary motor and primary sensory fields, with the premotor and first o rder sensory association areas occupying an intermediate position. Of the t halamic grays evaluated, those containing powerfully myelinated fiber tract s (e.g. centrum medianum, habenular complex) show the weakest immunolabelin g, whereas, less sturdily myelinated structures are highly immunoreactive. The fact that the immunostaining spectrum for normal alpha -synuclein is so broad, together with the fact that some thalamic sites actually are immuno negative leads to the following conclusions (1) alpha -synuclein, although present in the synaptic boutons of many nerve cells in the adult human CNS, is by no means ubiquitous there, and (2) neuronal types lacking the normal protein cannot generate the Parkinson's disease-specific filamentous patho logy. (C) 2000 Elsevier Science B.V. All rights reserved.