Regional, disease-specific reduction in CAPN1 activity in DLB, and inverse correlation with α-syn load in human post-mortem brain tissue. a α-syn and b α-syn-P129 immunopositive field fractions in DLB (there was no labelling in controls), and c α-syn and d α-syn-P129 levels in DLB and controls as measured by sandwich ELISA in brain tissue extracts, varied in a regional dependent-manner. The field fraction and level of α-syn-P129 were highest in the cingulate cortex. The α-syn field fraction was also highest in the cingulate cortex (and lowest in the thalamus). CAPN1 activity was significantly reduced in DLB in the e cingulate and f parahippocampal cortex but not in g frontal cortex or h thalamus. CAPN1 activity was increased in the f parahippocampal gyrus in AD but not in other regions. In a combined cohort, CAPN1 activity tended to correlate inversely with the levels of i-j α-syn, although this did not reach significance and significantly with k-l α-syn-P129 in the cingulate and parahippocampal cortex. In the cingulate cortex, CAPN1 activity correlated inversely with m α-syn and n α-syn-P129 in the DLB group alone. In a-h the horizontal bars indicate the mean value and SEM. In i-n the solid lines indicate best fit linear regression and the interrupted lines the 95% confidence intervals. In all of the panels, each point represents a separate brain. *P < 0.05 ***P < 0.001.