Non-Aβ component of Alzheimer's disease amyloid (NAC) revisited -: NAC and α-synuclein are not associated with Aβ amyloid

alpha-Synuclein (alpha SN), also termed the precursor of the non-A beta component of Alzheimer's disease (AD) amyloid (NACP), is a major component of Lewy bodies and Lewy neurites pathognomonic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). A fragment of alpha SN termed the non-A beta component of AD amyloid (NAC) had previously been identified as a constituent of AD amyloid plaques. To clarify the relationship of NAC and alpha SN with A beta plaques, antibodies were raised to three domains of alpha SN. All antibodies produced punctate labeling of human cortex and strong labeling of Lewy bodies. Using antibodies to alpha SN(75-91) to label cortical and hippocampal sections of pathologically proven AD cases, we found no evidence for NAC in A beta amyloid plaques. Double labeling of tissue sections in mixed DLB/AD cases revealed alpha SN in dystrophic neuritic processes, some of which were in close association with A beta plaques restricted to the CA1 hippocampal region, In brain homogenates alpha SN was predominantly recovered in the cytosolic fraction as a 16-kd protein on Western analysis; however, significant amounts of aggregated and alpha SN fragments were also found in urea extracts of SDS-insoluble material from DLB and PD cases. NAC antibodies identified an endogenous fragment of 6 kd in the cytosolic and urea-soluble brain fractions, This fragment may be produced as a consequence of alpha SN aggregation or alternatively may accelerate aggregation of the full-length alpha SN.