Characterization of the unique In Vitro effects of unsaturated fatty acids on the formation of amyloid β fibrils

Abstract

Accumulation of amyloid ß (Aß) peptides, the major component of amyloid fibrils in senile plaques, is one of the main causes of Alzheimer’s disease. Docosahexaenoic acid (DHA) is a fatty acid abundant in the brain, and is reported to have protective effects against Alzheimer’s disease, although the mechanistic effects of DHA against Alzheimer’s pathophysiology remain unclear. Because dietary supplementation of DHA in Aß precursor protein transgenic mice ameliorates Aß pathology and behavioral deficits, we hypothesize that DHA may affect the fibrillization and deposition of Aß. Here we studied the effect of different types of fatty acids on Aß fibril formation by in vitro Aß fibrillization assay. Formation of amyloid fibrils consists of two steps, i.e., the initial nucleation phase and the following elongation phase. We found that unsaturated fatty acids, especially DHA, accelerated the formation of Aß fibrils with a unique short and curved morphology in its nucleation phase, which did not elongate further into the long and straight, mature Aß fibrils. Addition of DHA afterwards did not modify the morphology of the mature Aß(1–40) fibrils. The short and curved Aß fibrils formed in the presence of DHA did not facilitate the elongation phase of Aß fibril formation, suggesting that DHA promotes the formation of “off-pathway” conformers of Aß. Our study unravels a possible mechanism of how DHA acts protectively against the pathophysiology of Alzheimer’s disease.

Polyunsaturated Fatty Acid Composition of Cerebrospinal Fluid Fractions Shows Their Contribution to Cognitive Resilience of a Pre-symptomatic Alzheimer’s Disease Cohort

“…Disruption of membrane components, including fatty acid composition, can alter interactions with these proteins. For example, physical measurements show that the ratio of saturated to PUFA influences how Aβ 42 binds to BACE (Cole and Frautschy, 2006;Grimm et al, 2011;Eto et al, 2019;Marwarha et al, 2019). Similar changes in fatty acids that we measured in CSF fractions, and their correlation with Aβ 42 and T-tau in our clinical groups confirm the role of fatty acids in AD severity and progression.…”

Omega-3 Fatty Acids and Vitamin D Decrease Plasma T-Tau, GFAP, and UCH-L1 in Experimental Traumatic Brain Injury

“…In contrast, plasma levels of DHA increased significantly (53.6%, P < 0.05) in rats consuming AIDM diets, and DHA levels in the frontal cortex increased by 22.9% (P < 0.05), from 9.55 to 11.74% of total PUFAs. Previous reports indicate that DHA contributes to clearance of amyloid-β in the brain (80,81), and both DHA and DHA-derived metabolites such as neuroprotectin D1 (82) and resolvins (83) protect against neurodegeneration. Likewise, EPA can directly inhibit prostaglandin synthesis and be converted to inflammation resolving metabolites, e.g., resolvin E1, but both having a lower bioactivity than that of DHA (84).…”

Conflito Entre O Direito À Honra E O Direito À Informação Na Perspectiva Da Responsabilidade Midiática

“…Os ácidos graxos ômega-3 atuam na segunda fase, já que interage com βA e dificultam sua agregação, atrapalhando o crescimento das fibrilas, deixando-as curtas e curvas (ETO et al, 2019). Influenciam, também, na redução do estresse oxidativo, que ocorre pelo aumento de radicais livres e, como consequência, preservam a organização dos microtúbulos (ARAYA-QUINTANILLA et al, 2020).…”