Objective: To study associations of cerebrospinal fluid (CSF) amino acids and monoamine metabolites with motor and non-motor features in dementia with Lewy bodies (DLB) compared with Alzheimer’s dementia (AD) and healthy controls.

Background: Motor and non-motor aspects of daily experiences may reflect amino acid and monoamine metabolism in dementia.

Methods: Consecutive outpatients with probable DLB (fourth consensus report of the DLB Consortium) were paired with outpatients with late-onset AD by gender, Clinical Dementia Rating (CDR) and Mini-Mental State Examination scores, and with healthy controls by gender and age (±1 year). Genotyping for rs7412 & rs429358 was undertaken with TaqMan® Real-Time PCR technology. CSF amino acid (aspartate, glycine, glutamine, glutamate, taurine, GABA) and monoamine metabolite (HVA, 5-HIAA, VMA, MHPG, L-DOPA) concentrations were assessed by reverse-phase high-performance liquid chromatography, and correlated with the Schwab and England Scale (S&E), the MDS-UPDRS parts I/II/III, and the Hoehn and Yahr stages (H&Y).

Results: Twenty participants with DLB (77.00±9.0 years-old, CDR sum-of-boxes 10.15±3.7, nine APOE-ε4 carriers) were paired with twenty participants with AD (80.35±5.9 years-old, CDR sum-of-boxes 9.43±3.5, nine APOE-ε4 carriers) and twenty controls (77.15±9.0 years-old, CDR sum-of-boxes 0.25±0.5, three APOE-ε4 carriers). Associations for APOE-ε4 carriers (p<0.0001): glutamine and glutamate associated with S&E in DLB and AD; aspartate and GABA associated with S&E in AD; taurine associated with S&E in DLB, and with MDS-UPDRS-I in AD; VMA inversely associated with S&E in DLB; glutamine inversely associated with MDS-UPDRS-II in AD, and inversely associated with H&Y in DLB. Associations for APOE-ε4 non-carriers (p<0.0001): glutamate associated with MDS-UPDRS-I in DLB and AD; L-DOPA associated with MDS-UPDRS-I in AD; aspartate and GABA associated with MDS-UPDRS-I in DLB; aspartate, glycine, glutamate and GABA associated with MDS-UPDRS-II in DLB; MHPG and L-DOPA associated with MDS-UPDRS-III in DLB; L-DOPA, aspartate, glutamate, taurine and GABA associated with H&Y in DLB; glutamate and taurine inversely associated with S&E in DLB and AD; aspartate inversely associated with S&E in DLB; MHPG inversely associated with MDS-UPDRS-I in DLB; VMA and the HVA/5-HIAA ratio inversely associated with MDS-UPDRS II & III in DLB; glycine inversely associated with H&Y in DLB.

Conclusions: Neurotransmitter dysfunction differentially affects motor and non-motor features in dementia syndromes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-and-non-motor-correlates-of-apoe-%ce%b54-mediated-cerebrospinal-fluid-concentrations-of-amino-acids-and-monoamine-metabolites-in-dementia-with-lewy-bodies-compared-with-alzheimers-demen/