Distribution Of Lewy Body-related Pathology In Postmortem Human Brain Tissue And The Correlation With Antemortem Cognition Performance

BACKGROUNDLewy body disease(LBD)is a common group of neurodegenerative diseases characterized by Lewy body(LB)formation in neuronal somata and axons.Parkinson disease is the most common type of LBD,and is pathologically characterized by the loss of neurons and aggregated ?-synuclein in LB and Lewy neurites(LN).Motor-related symptoms such as tremor and akinesia always presented at the early stage of the disease.With the spread of ?-synuclein from brainstem to the cortical,cognitive impairment usually occurs.AD-related pathological changes in PD patients and ApoE ?4 carriers may exacerbate cognitive dysfunction.However,knowledge about the distribution of Lewy-related pathology(LRP)and the clinicopathological correlations of PD and PD cognitive defects based on the study of Chinese human brain bank is still remarkably limited.OBJECTIVEThis study aimed to investigate the distribution of Lewy-related pathology and the correlations between the antemortem clinical cognitive performances and the postmortem neuropathological changes in the brains with LRP recruited in the CAMS/PUMC Human Brain Bank.METHODSA total of 76 human brains with antemortem cognitive status information[Everyday Cognition(ECog)]and ABC pathological score of Alzheimer's disease(AD)were collected through the willed donation program in CAMS/PUMC Human Brain Bank.LB pathological changes were evaluated with Braak staging of Lewy body disease.ApoE genotyping was also performed.The clinicopathological relationship was analyzed with non-parameter method with SPSS 24.0.RESULTSThe sensitivity of PD diagnosis according to the medical history in this study was 66.7%and the specificity was 98.6%.The false negative rate(FNR)was 1.4%whereas the false positive rate(FPR)was 33.3%for the current diagnosis criteria of PD.The Braak staging of LRP may correlate with cognitive dysfunction in PD patients.With the growth of Braak staging,the Global ECog score and ECog domain scores mounted up(Global ECog score:p = 0.091;Memory:p = 0.079;Language:p = 0.068;Visuospatial:p =0.060;Planning:p = 0.255;Organization:p = 0.064;Divided attention:p = 0.129).Cognitive dysfunction(Dementia and Mild Cognitive dysfunction,MCI)in PD(PD-D or PD-MCI)is common.AD related pathological changes and ApoE ?4 may promote the cognitive dysfunction in PD patients.CONCLUSIONRegarding the current diagnostic criteria,our knowledge about PD and PD-related cognitive impairment may not be enough.The AD-related pathological changes and ApoE s4 may correlate with cognitive impairment in PD.