Lewy Body Pathology and Alzheimer Disease in Down Syndrome

Abstract Introduction/Objective Aging adults with Down syndrome (DS) develop Alzheimer disease neuropathology (AD) by the age of 40 years, primarily due to the overexpression of the amyloid precursor protein on chromosome 21. Lewy bodies (LBs), containing alpha-synuclein protein, are observed in 7-60% of AD patients in the amygdala and in cortex. Prior DS studies (n=20-56 cases) find the frequency of LB pathology to range between 8-50% of cases being affected. We hypothesized that LB pathology would also be present in DS brain with similar locations and prevalence to AD. Thus, we evaluated the frequency of LB in our UCI cohort of DS cases that we have collected over the past 25 years. Methods/Case Report Neuropathology reports from 55 cases with DS from the UCI-ADRC were included in this study. Cases were stained for beta-amyloid, phosphor-tau, alpha-synuclein and TDP-43 as per NACC protocols (one case each v7,8,9 and three v11). Results (if a Case Study enter NA) We identified 6 cases (10.9%), all male, with a mean age of 57 years (SD=3) that showed LB and/or Lewy neurites. LB pathology was classified as amygdala predominant in 3 cases, brainstem predominant in one, intermediate/transitional in one, and diffuse/neocortical in one. Five cases were BRAAK stage 6 and one was stage 5. Five cases had CERAD neuritic plaque score C and one case had a B score. Two of 3 cases were Thal phase 5, and one was phase 4. The case with diffuse/neocortical LB pathology demonstrated hippocampal sclerosis. Conclusion The observation that all our LB positive cases were male may reflect a sample bias. In our study, Lewy pathology was most common in amygdala but other sites of involvement are seen similar to a prior DS study and AD studies. Prior DS studies (n=20-56 cases) find the frequency of LB pathology to range between 8-50% of cases being affected. The prevalence of LB in our DS cohort (10.9%) is in the low end of the range seen in other DS and AD studies.