Abstract Body

The defining neuropathological features of Alzheimer's disease (AD) are amyloid-β (Aβ) plaques and hyperphosphorylated tau (tau) in the form of neurofibrillay tangles and neuropil threads while Lewy body diseases (LBD) are characterised by Lewy bodies and Lewy neurites composed of α-synuclein (α-syn) depositions. However, over 90% of clinical LBD cases show AD type pathology in addition to Lewy pathology and AD cases often show additional Lewy pathology.

True mixed dementia is diagnosed if the severity of both Lewy and AD pathology is so severe that each could be the neuropathological correlate of clinical dementia. Using quantitative measures on the burden of Aβ, tau and, α-syn in such mixed AD/LBD cases we found that both the amount and the topographical distribution of pathological protein aggregates differed between clinical AD and DLB phenotypes. In particular the distribution of tau in in clinical AD cases in such mixed AD/DLB cases was similar to the one observed in pure AD cases without Lewy pathology, while clinical DLB cases had comparatively less hippocampal tau.

Large scale clinico-pathological correlative studies using a quantitative methodology are warranted to further elucidate the neuropathological correlate of clinical symptoms in cases with mixed AD/LBD pathology.