Relationship of phosphorylated α-synuclein and tau accumulation to Aβ deposition in the cerebral cortex of dementia with Lewy bodies

alpha-Synuclein accumulated in the brain of dementia with Lewy bodies (DLB) is phosphorylated at serine 129 (p alpha-synuclein). We investigated the accumulation of pa-synuclein in the brains of patients with DLB and Alzheimer's disease (AD). We employed 18 DLB patients with neocortical Lewy body type pathology (nLBTP) with or without AD. We also employed the same number of AD cases without significant nLBTP. We refer to the former group as the nLBTP group and to the latter as the AD type pathology (ADTP) group. In the nLBTP group, p alpha-synuclein positive neurite pathology such as threads and dots occurs in all layers of the temporal neocortex. It was comparable in degree with tau pathology in AD. Fifteen cases in the nLBTP group were associated with A beta deposition that meets the CERAD plaque score C and one case with a score B. In these plaque-associated cases, the severity of pa-synuclein pathology was related to the degree of A deposition. In the cases with relatively moderate A deposition, tau pathology was disproportionately mild in the nLBTP group, while the total of tau and pa-synuclein pathology was proportionate to A beta deposition in both the nLBTP and ADTP groups. Our results support the ideas that there is an overlap in the pathology between AD and DLB and that A promotes accumulation of both alpha-synuclein and tau. The procession from A to neurite pathology in the cerebral cortex of AD and DLB may be unifiable. (c) 2007 Elsevier Inc. All rights reserved.