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

Article type: Research Article

Authors: de Oliveira, Fabricio Ferreira^{a; *} | Miraldo, Marjorie Câmara^a | de Castro-Neto, Eduardo Ferreira^a | de Almeida, Sandro Soares^b | Matas, Sandro Luiz de Andrade^a | Bertolucci, Paulo Henrique Ferreira^a | Naffah-Mazzacoratti, Maria da Graça^a

Affiliations: [a] Department of Neurology and Neurosurgery Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil | [b] Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Correspondence: [*] Correspondence to: Fabricio Ferreira de Oliveira, MD, MSc, PhD, Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, Rua Botucatu 740, Vila Clementino, CEP 04023-900, São Paulo, SP, Brazil. Tel.: +55 (+11) 5576 4139; Fax.: +55 (+11) 5575 5240; E-mail: [email protected].

Abstract: 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-β (Aβ)42, Aβ40, Aβ38, total tau, phospho-tau Thr181, α-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOE ɛ4 carrier status. Results:Overall, 27 patients with DLB (78.48±9.0 years old, eleven APOE ɛ4 carriers) were paired with 27 patients with AD (81.00±5.8 years old, twelve APOE ɛ4 carriers) and 27 controls (78.48±8.7 years old, four APOE ɛ4 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 ɛ4 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 Aβ and tau biomarkers predicting neuropsychiatric symptoms when associations with isolated biomarkers were not significant. At the end, APOE ɛ4 carrier status influenced amyloidogenesis and tau pathology in DLB and in AD, and axonal degeneration only in DLB.

Keywords: Alzheimer’s disease, APOE, behavioral symptoms, biomarkers, cerebrospinal fluid, dementia, Lewy body dementia, neuropsychiatry

DOI: 10.3233/JAD-210272

Journal: Journal of Alzheimer's Disease, vol. 81, no. 3, pp. 1295-1309, 2021