Dementia & MCI Alpha-synuclein biology
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Alzheimer-type co-pathology (tau and amyloid-β) promotes alpha-synuclein fibrilization synergistically and is among the strongest independent predictors of dementia in PD beyond Lewy body burden alone.
Tau and alpha-synuclein promote the fibrilization of each other in a mutually reinforcing cycle; patients with higher Alzheimer co-pathology burden develop cognitive impairment faster and more severely, with neocortical alpha-synuclein pathology and Alzheimer co-pathology acting as independent contributors to PD dementia.