It is increasingly clear that the normal protein alpha-synuclein is in some 
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 selectively in the 
form of filamentous inclusion bodies during certain progressive 
neurodegenerative disorders, such as familial and sporadic Parkinson's disease. 
By having the antibody AFshp raised specifically to alpha-synuclein to label 
Parkinson disease-specific Lewy bodies and Lewy neurites as well as synaptic 
boutons containing the unaltered protein, an initial attempt is made to map the 
overall distribution pattern and describe the staining behavior of the 
immunoreactive punctae in select regions of the prosencephalon. Neocortical 
immunolabeling is most prominent in the prodigious, but incompletely myelinated, 
association fields and faintest in the heavily myelinated primary motor and 
primary sensory fields, with the premotor and first order sensory association 
areas occupying an intermediate position. Of the thalamic grays evaluated, those 
containing powerfully myelinated fiber tracts (e.g. centrum medianum, habenular 
complex) show the weakest immunolabeling, 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 immunonegative 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 pathology.