The Division of Neuroscience, NIA cosponsored this exploratory workshop with the National Institute of Neurological Disorders and Stroke. Alzheimer’s disease and Lewy Body disease (LBD) are perhaps the most common causes of dementia in the elderly. There is a substantial clinical overlap among the dementias associated with Alzheimer's disease, LBD, and Parkinson's disease (PD). Dementia develops in all patients with Alzheimer’s disease and LBD and in approximately 20 to 30 percent of patients with PD.
A growing body of evidence suggests a nonbeta amyloid component of Alzheimer's disease plaques (NACP)—also termed alpha-synuclein—contributes to neurodegenerative processes in Alzheimer's disease, LBD, and PD. Alpha-synuclein, a synaptic protein, was first associated with a neurodegenerative disease when NACP was isolated from a brain with Alzheimer’s disease, and it was determined antibodies to NACP recognize a significant percentage of diffuse and mature plaques and the Lewy bodies in Alzheimer's disease, LBD, and PD. In addition to alpha synuclein, the Lewy bodies contain ubiquitin and other proteosomal subunits. Intracellular degradation of many proteins involves their conjugation with ubiquitin and enzymatic cleavage to amino acid constituents in the proteasome. The ubiquitins are a family of scavenger proteins found throughout the brain, and their presence in the Lewy bodies may result from an attempt by ubiquitin to break up the accumulated alpha-synuclein.
This workshop examined the basic biology of alpha synuclein, the formation of Lewy Bodies, and their role in the dementias associated with Alzheimer's disease, LBD, and PD.
Dr. Creighton Phelps