Digital mapping of Lewy bodies and neurites in alpha-synuclein stained large cerebral hemispheric sections from three patients with dementia with Lewy bodies showing psychotic manifestations: A pilot study.

Abstract Background Dementia with Lewy bodies (DLB) is one of the major neurodegenerative diseases and a clinical diagnosis is made based on the fourth consensus report on DLB. However, clinicopathological features of DLB are variable among cases. Methods We analyzed three autopsy-proven cases of DLB (patients 1–3). Their clinical features were variable in spite of their pathological commonality. The entire hemispheric sections were stained for phosphorylated alpha-synuclein (aS), digitized, and each aS positive lesion was mapped using a virtual slide system. Results The three patients were clinically diagnosed as having DLB. However, patient 1 exhibited amnesia and misrecognition, while patient 3 exhibited abnormal behavior in addition to dementia. Therefore, both patients 1 and 3 did not fulfill the clinical criteria of DLB, in contrast to patient 2. In spite of the clinical heterogeneity, Lewy pathology was similar in patients 1, 2, and 3. Additionally, patient 1 exhibited less frequent Lewy neurites of the amygdala and entorhinal cortex, and less frequent neurofibrillary tangles and senile plaque as compared to patient 2. On the other hand, the Lewy pathology of patient 3 extended far beyond those of patients 1 and 2, wherein the superior to middle frontal cortices, insular cortex, and lentiform nucleus were severely affected by Lewy pathology. Conclusions Clinical features could be variable among autopsy-proven cases of DLB. Furthermore, we show that the accent of Lewy pathology differs according to the variability of the clinical symptoms. This method will provide a comprehensive strategy to analyze wide-spread aS lesions scattered throughout the entire cerebral hemisphere and help determine the corresponding pathological lesions responsible for the clinical variability of neurodegenerative disorders, including DLB.