**Brain Lipids in the Pathophysiology and Treatment of Alzheimer's Disease**

Manuel Torres, Xavier Busquets and Pablo V. Escribá

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64757

#### **Abstract**

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126 Update on Dementia

Alzheimer's disease (AD) is a neurodegenerative disorder that causes severe and progressive cognitive impairment. The discovery of specific mutations related to AD supported the amyloid cascade hypothesis, which postulates that the accumulation of the amyloid-β (Aβ) peptide triggers neuronal death and dementia. However, most drugs that aim to prevent Aβ accumulation or tau phosphorylation have consistently failed in clinical trials. This would suggest that the amyloid pathology lies down‐ stream of (an)other cellular event(s) that is/are responsible for AD pathogenesis. In this context, several lipid alterations have been described in the brain and in peripheral fluids of patients with AD, suggesting the involvement of lipids in the etiology of this condition. Indeed, the central nervous system (CNS) has the highest lipid content in the body, next to adipose tissue, and it is thought that normalization of brain membrane lipid levels would revert AD-related pathogenic events. In this sense, novel hydroxy‐ lated derivatives of docosahexaenoic acid (DHA) such as natural resolvins or synthet‐ ic hydroxy-DHA (HDHA, DHALifort) can modulate membrane lipid composition and show remarkable beneficial effects on AD hallmarks, such as prevention of amyloid production and tau phosphorylation, and cognitive restoration in animal models. Therefore, normalization of the neuronal lipid environment by hydroxyl-DHA and/or other lipids may constitute a promising therapy for AD treatment, memory loss and, possibly, other types of dementia.

**Keywords:** Alzheimer's disease, neurodegeneration, neuroregeneration, hydroxy-DHA, amyloid, tau, neurite dystrophy, inflammation, brain lipids, cholesterol, sphin‐ golipids, lipid rafts, omega-3 PUFAs, HDHA, DHALifort, resolvins, neuroprotectins, lipid biomarkers

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