F2‐02‐05: Four siblings with Variable Clinical and Pathological Characteristics of Alzheimer's and Lewy Body Disease

Background: Lewy related pathology (LRP) is observed in number of neurodegenerative diseases including Parkinson disease, dementia with Lewy bodies, and Alzheimer’s disease (AD). Of interest, in some of these diseases the presence and severity of LRP is quite variable, even within dominantly inherited familial disease. The current report examines LRP and related pathologic changes in 4 siblings with a familial neurodegenerative process. Methods: Clinical records were reviewed for 4 siblings from a family with a history of late-onset dementia. In addition, detailed neuropathologic evaluation was performed in all 4 siblings, including assessment of LRP and pathologic changes associated with AD and frontotemporal dementia (neurofibrillary tangles, neuritic plaques, TDP43).Results: Family history was positive for dementia in the mother and maternal uncle. Four of seven siblings were affected. Clinical characteristics included dementia at onset in 3 of 4 siblings, while the remaining sibling was diagnosed with Parkinson disease. One sibling with dementia at onset had motor parkinsonism and hallucinations. The single sibling with parkinsonism at onset was responsive to dopaminergic therapy and had evidence of cognitive impairment just prior to death (7 years after onset of motor parkinsonism). Mean age at onset was 80.5 years (range of 78 to 82 years). Neuropathologic examination revealed AD in the three siblings with dementia at onset, however 2 of these also had neocortical LRP. The sibling with clinical PD had neocortical LRP, but Braak stage IV neurofibrillary tangles and CERAD stage A neuritic plaques. APOE genotype was 3/3 for 2 siblings and 3/4 for one. LRRK2 mutations were not found. Conclusions: We describe an intriguing family with a variable clinical picture within a single sibship. One sibling fulfilled clinical criteria for Parkinson disease, while the 3 others had clinical histories consistent with AD or dementia with Lewy bodies. Pathologic change generally correlated well with the clinical syndrome in each sibling. These findings, along with previous observations, point to substantial variability of clinical syndrome and pathology in many diseases with LRP. Further study of familial diseases characterized by LRP may elucidate the genetic and environment factors that underlie this variability. F2-02-06 MIXED ALZHEIMER’S AND LEWY BODY DISEASE PATHOLOGY PATTERNS