Molecular Medicine and Diagnostics

Biography

Biography: Katrin Beyer

Abstract

Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are synucleinopathies and DLB is the most frequent cause of dementia after Alzheimer’s diseases (AD). All three show an important neuropathological overlap and especially DLB is difficult to diagnose. DLB results from complex interactions among different susceptibility genes and environmental risk factors with particular impact for each individual. Although all patients fulfill diagnostic criteria fitting within certain spectrum of symptoms and disease course, the primary cause of DLB may not be the same in all cases. So far, alpha-synuclein pathology caused by alpha-synuclein oligomerization and further aggregation, and cholinergic deficit that is even more pronounced in DLB than in AD brains, have been unequivocally involved in DLB pathogenesis. But even these main pathologic processes reach different degrees of severity in each patient and are accompanied by other pathological events. Similar severity degrees of the various processes define molecular subgroups of DLB, and these are detectable independently each one by its own biomarkers. We have recently described two molecular subgroups of DLB. One of them comprises about 30% of all patients and is characterized by the absence of beta-synuclein in cortical regions. The other constitutes around 10% with cortical butyrylcholinesterase diminution. For both molecular defects we have identified the associated genetic biomarkers useful for the early detection of these patients. Our results also indicate that DLB can develop as primary or secondary synucleinopathy. In the latter, alpha-synuclein pathology would develop after action of primary alterations such as lysosomal dysfunction or transcriptional deregulation.