Associations of Alzheimer’s Disease Neuropathologic Changes with Clinical Presentations of Parkinson’s Disease

Background: Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the two most prevalent neurodegenerative diseases associated with age. Pathological studies have shown that these two diseases share a certain degree of neuropathological overlap. AD neuropathologic change contributes to cognitive impairment in PD. However, the impact of AD pathology on other clinical phenotypes in PD remains largely unknown. Objective: Herein we aimed to assess the impact of co-occurring AD neuropathologic change on the clinical phenotypes of PD. Methods: We examined 46 autopsy brains of PD patients and available clinical information to retrospectively assess the effects of comorbid AD pathology on dementia, hallucinations, and dyskinesia commonly seen in advanced PD. Results: AD neuropathology significantly increased the risk of hallucinations and dementia, but not dyskinesia in PD patients. Surprisingly, diffuse Lewy body pathology, but not AD pathology, was associated with the occurrence of dementia and hallucinations. Most importantly, we reported that the severity of neuronal loss in the locus coeruleus (LC), but not the severity of neuronal loss in the substantia nigra (SN), was associated with the occurrence of dyskinesia in advanced PD patients, while neither Lewy body scores in SN nor LC had significant effects. Conclusion: We show for the first time that neuronal loss in LC contributes to dyskinesia. Understanding the relationships between the two distinct pathologies and their relevant clinical phenotypes will be crucial in the development of effective disease-modifying therapies for PD.