Abnormal Neurites Containing C-Terminally Truncated α-Synuclein Are Present in Alzheimer's Disease without Conventional Lewy Body Pathology

The pathological hallmark of Parkinson s disease and diffuse Lewy body disease (DLBD) is the aggregation of alpha synuclein (alpha syn) in the form of Lewy bodies and Lewy neurnes Patients with both Alzheimer s disease (AD) and cortical Lewy pathology represent the Lewy body variant of AD (thy) and constitute 25% of AD cases C terminally truncated forms of alpha syn enhance the aggregation of alpha syn in vitro To investigate the presence of C terminally truncated alpha syn in DLBD AD, and thy we generated and validated polyclonal antibodies to truncated alpha syn ending at residues 110 (alpha syn110) and 119 (alpha syn119) two products of 20S proteosome mediated endoproteolytic cleavage Double immunofluorescence staining of the cingulate cortex showed that alpha syn110 and alpha syn140 (full length) aggregates were not colocalized in LBV All aggregates containing alpha syn140 also contained alpha syn119 how ever some aggregates contained alpha syn119 without alpha syn140 suggesting that alpha syn119 may stimulate aggregate formation Immunohistochemistry and image analysis of tissue microarrays of the ungulate cortex from patients with DLBD (n = 27) LBV (n = 27) and AD (n = 19) and age matched controls (n = 15) revealed that AD is also characterized by frequent abnormal neurites containing alpha syn119 Notably these neurites did not contain alpha syn ending at residues 110 or 122 140 The presence of abnormal neurites containing alpha syn119 in AD without conventional Lewy pathology suggests that AD and Lewy body disease may be more closely related than previously thought (Am J Pathol 2010 177 3037-3050 DOI 10 2353/ajpath 2010 100552)