Discovery of new lesions in neurodegenerative diseases with monoclonal antibody techniques: is there a non-amyloid precursor to senile plaques?

The manuscript by Schmidt et al reports that antibodies generated to paired helical filaments (AMY antibodies) unexpectedly labeled novel non-amyloid, plaque-like structures (AMY plaques) in aged and Alzheimer's disease brains. The full disclosure of the nature of these lesions awaits additional structural and biochemical studies, but at first glance there are interesting parallels between AMY plaques and recently described lesions composed of glia and glia-associated proteoglycans in brains of aged mice. The increasing recognition of the role of proteoglycans in paired helical filaments formation makes proteoglycans or their associated molecules attractive candidates for AMY-immunoreactive proteins. The relationship of AMY plaques to age-related glial changes that some have speculated may be precursors to senile plaques remains to be determined, as is the relationship of AMY plaques to more widely recognized amyloid-containing plaques. Future studies will determine whether AMY plaques are non-amyloid precursors to senile plaques or if they represent an independent type of structural lesion in the Alzheimer's disease brain. Ultimately, the clinical significance of AMY plaques will depend upon their characterization in brains of prospectively studied subjects.