The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease

Abstract

Introduction: Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear. Methods: The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC-FID. The MCI subjects were followed up for 58 ± 12.5 months. Results: In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI-to-AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI-to-AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI-to-AD progression, respectively. Discussion: The circulating LFA is involved in the pathogenesis and progression of AD. Highlights: The lipidome fatty acid profile in CSF and plasma was markedly different. Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease. In plasma, higher levels of oleic acid were associated with a reduced risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI-to-AD progression.

Government of Catalonia,Grant/Award Number:PERIS 2019 SLT008/18/00050; Ministerio de Ciencia, Innovación y Universidades; European Union ’Awaytobuild Europe’, Grant/Award Numbers: RTI2018-099200-B-I00, PID2023-152233OB-I00; Diputació de Lleida, Grant/Award Number: PP10605-PIRS2021; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: PID2020-119978RB-I00; CIBERNED, Alzheimer’s Association, Grant/Award Number:AARG-NTF-22-924702; Junta de Andalucía, Grant/Award Number: PY20_00858; Andalucía-FEDER Program, Grant/Award Number: UPO-1380913; Agency for Management of University and Research Grants, Grant/Award Number: 2021SGR 00761; Agency for Management of University and Research Grants and the European Social Fund, Grant/Award Number: FI_B100153; Agency for Management of University and Research Grants and the European Social Fund, Grant/Award Number: 2021SGR00990