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(American Journal of Pathology. 1999;155:1173-1181.)
© 1999 American Society for Investigative Pathology

Regular Articles

Non-Aß Component of Alzheimer's Disease Amyloid (NAC) Revisited

NAC and {alpha}-Synuclein Are Not Associated with Aß Amyloid

Janetta G. Culvenor*, Catriona A. McLean*, Sally Cutt*, Bruce C. V. Campbell*, Fran Maher*, Pekka Jäkälä{dagger}{ddagger}, Tobias Hartmann{dagger}, Konrad Beyreuther{dagger}, Colin L. Masters* and Qiao-Xin Li*

From the Department of Pathology,*
The University of Melbourne, Parkville, Victoria, Australia; the Center for Molecular Biology,{dagger}
The University of Heidelberg, Heidelberg, Germany; and the University of Kuopio and University Hospital of Kuopio,{ddagger}
Kuopio, Finland

{alpha}-Synuclein ({alpha}SN), also termed the precursor of the non-Aß 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-Aß 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 Aß 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 Aß 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 Aß 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.




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