Lipids and Alzheimer’s Disease

Kao, Yu-Chia; Ho, Pei‐Chuan; Tu, Yuan‐Kun; Jou, I‐Ming; Tsai, Kuen‐Jer

doi:10.3390/ijms21041505

Cited by 301 publications

(278 citation statements)

References 307 publications

(351 reference statements)

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“…However, if APP interacts with ApoE and tau on a lipid raft with an atypical lipid composition, signal transduction may be disrupted, promoting the formation of AB aggregates. Other alterations include reductions in unsaturation of FA in AD patients, as compared to controls (Kao et al, 2020). Lipid raft aging also appears to exhibit gender differences, such that women had more severe changes in lipid raft composition as compared to men.…”

Section: The Intersection Of Lipids App Processing and Ad Pathologymentioning

confidence: 99%

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

2020

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Lipids constitute the bulk of the dry mass of the brain and have been associated with healthy function as well as the most common pathological conditions of the brain. Demographic factors, genetics, and lifestyles are the major factors that influence lipid metabolism and are also the key components of lipid disruption in Alzheimer's disease (AD). Additionally, the most common genetic risk factor of AD, APOE 4 genotype, is involved in lipid transport and metabolism. We propose that lipids are at the center of Alzheimer's disease pathology based on their involvement in the blood-brain barrier function, amyloid precursor protein (APP) processing, myelination, membrane remodeling, receptor signaling, inflammation, oxidation, and energy balance. Under healthy conditions, lipid homeostasis bestows a balanced cellular environment that enables the proper functioning of brain cells. However, under pathological conditions, dyshomeostasis of brain lipid composition can result in disturbed BBB, abnormal processing of APP, dysfunction in endocytosis/exocytosis/autophagocytosis, altered myelination, disturbed signaling, unbalanced energy metabolism, and enhanced inflammation. These lipid disturbances may contribute to abnormalities in brain function that are the hallmark of AD. The wide variance of lipid disturbances associated with brain function suggest that AD pathology may present as a complex interaction between several metabolic pathways that are augmented by risk factors such as age, genetics, and lifestyles. Herewith, we examine factors that influence brain lipid composition, review the association of lipids with all known facets of AD pathology, and offer pointers for potential therapies that target lipid pathways.

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Section: The Intersection Of Lipids App Processing and Ad Pathologymentioning

confidence: 99%

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

2020

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“…Of the five FFAs detected in our study, DHA had a distinct distribution in the epithelium of the vermilion (Figure 4), which made a remarkable difference between the vermilion and the skin. DHA is an important omega-3 PUFA in the human body and is well known for its multiple beneficiary effects [20,24,25]. In the vermilion, DHA may play a role as an antioxidant and thus contribute to the anti-aging of the lip.…”

Section: Discussionmentioning

confidence: 99%

Higher Accumulation of Docosahexaenoic Acid in the Vermilion of the Human Lip than in the Skin

Mamun

Sato

Naru

et al. 2020

IJMS

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The vermilion of the human lip is a unique facial area because of certain distinguishing features from the adjacent tissues such as the white lip (skin) and oral mucosa. However, the distinction in terms of molecular distribution between the vermilion and skin has remained unexplored. Therefore, we aimed to map the human lip by mass spectrometry imaging to gain understanding of the free fatty acid distribution in the vermilion. The lip specimens trimmed off during cheiloplasty were analyzed using desorption electrospray ionization–mass spectrometry imaging. Distributions of two monounsaturated fatty acids and three polyunsaturated fatty acids were observed in the human lip tissue: palmitoleic acid (POA) and oleic acid (OA) and linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA), respectively. Although POA, OA, LA, and AA were differentially distributed across the vermilion and skin, DHA showed a higher accumulation in the epithelium of the vermilion compared to that in the skin. Our results clearly demonstrated the difference in fatty acid distributions between the vermilion and skin. The highly abundant DHA in the epithelium of the vermilion may have an antioxidant role and may thus protect the lip from aging. Our findings can provide a novel strategy for treating lip disorders.

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“…The balance between oxidant sources and oxidant scavengers gives rise to pathologically high or physiologically low levels of ROS. High levels of ROS induce oxidative stress, leading to advanced glycation end-products (AGE) accumulation [20], insoluble protein aggregation [21], lipid peroxidation [22] and nucleic acid damage [23]. Low levels of ROS activate cellular signaling, such as apoptosis [24], cell proliferation and differentiation [25], metabolic regulation [26] and pathogen defense [27].…”

Section: Oxidative Stress and Agingmentioning

confidence: 99%

Pro-Aging Effects of Xanthine Oxidoreductase Products

et al. 2020

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The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.

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Lipids and Alzheimer’s Disease

Cited by 301 publications

References 307 publications

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

Higher Accumulation of Docosahexaenoic Acid in the Vermilion of the Human Lip than in the Skin

Pro-Aging Effects of Xanthine Oxidoreductase Products

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