Associations of Neuropsychiatric Features with Cerebrospinal Fluid Biomarkers of Amyloidogenesis and Neurodegeneration in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People

Background: Behavioral features may reflect proteinopathies predicting pathophysiology in neurodegenerative diseases. Objective: We aimed to investigate associations of cerebrospinal fluid biomarkers of amyloidogenesis and neurodegeneration with neuropsychiatric features in dementia with Lewy bodies (DLB) compared with late-onset Alzheimer's disease (AD) and cognitively healthy people. Methods: Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive scores, and with cognitively healthy controls according to sex and age to investigate associations of cerebrospinal fluid amyloid-beta (A beta)(42), A beta(40), A beta(38), total tau, phospho-tau Thr181, alpha-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOE epsilon 4 carrier status. Results: Overall, 27 patients with DLB (78.48 +/- 9.0 years old, eleven APOE epsilon 4 carriers) were paired with 27 patients with AD (81.00 +/- 5.8 years old, twelve APOE epsilon 4 carriers) and 27 controls (78.48 +/- 8.7 years old, four APOE epsilon 4 carriers); two thirds were women. Behavioral burden was more intense in DLB. Biomarker ratios reflecting amyloidogenesis and neurodegeneration in DLB were more similar to those in AD when patients carried APOE epsilon 4 alleles. After corrections for false discovery rates, the following associations remained significant: in DLB, dysphoria was associated with tauopathy and indirect measures of amyloidogenesis, while in AD, agitation, and night-time behavior disturbances were associated with tauopathy, and delusions were associated with tauopathy and indirect measures of amyloidogenesis. Conclusion: Biomarker ratios were superior to A beta and tau biomarkers predicting neuropsychiatric symptoms when associations with isolated biomarkers were not significant. At the end, APOE epsilon 4 carrier status influenced amyloidogenesis and tau pathology in DLB and in AD, and axonal degeneration only in DLB.