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

Abstract

It is increasingly clear that the normal protein α-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 α-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 α-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 α-synuclein is so broad, together with the fact that some thalamic sites actually are immunonegative leads to the following conclusions (1) α-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.