Dataset Information

Lipids and brain inflammation in APOE4-associated dementia.

ABSTRACT:

Purpose of review

To highlight recent developments in studying mechanisms by which the apolipoprotein E4 (APOE4) allele affects the metabolism of brain lipids and predisposes the brain to inflammation and Alzheimer's disease (AD) dementia.

Recent findings

APOE4 activates Ca2+ dependent phospholipase A2 (cPLA2) leading to changes in arachidonic acid (AA), eicosapentaenoic acid and docosahexaenoic acid signaling cascades in the brain. Among these changes, the increased conversion of AA to eicosanoids associates with sustained and unresolved chronic brain inflammation. The effects of APOE4 on the brain differ by age, disease stage, nutritional status and can be uncovered by brain imaging studies of brain fatty acid uptake. Reducing cPLA2 expression in the dementia brain presents a viable strategy that awaits to be tested.

Summary

Fatty acid brain imaging techniques can clarify how changes to brain polyunsaturated fatty acid metabolism during the various phases of AD and guide the development of small molecules to mitigate brain inflammation.

SUBMITTER: Duro MV

PROVIDER: S-EPMC8769806 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Lipids and brain inflammation in APOE4-associated dementia.

Duro Marlon V MV Ebright Brandon B Yassine Hussein N HN

Current opinion in lipidology 20220201 1

<h4>Purpose of review</h4>To highlight recent developments in studying mechanisms by which the apolipoprotein E4 (APOE4) allele affects the metabolism of brain lipids and predisposes the brain to inflammation and Alzheimer's disease (AD) dementia.<h4>Recent findings</h4>APOE4 activates Ca2+ dependent phospholipase A2 (cPLA2) leading to changes in arachidonic acid (AA), eicosapentaenoic acid and docosahexaenoic acid signaling cascades in the brain. Among these changes, the increased conversion of ...[more]

PMID: 34907965

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Project description:Aim/backgroundThis research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer's disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer's disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2-3 years), brain cell inflammation can be demonstrated as the cause of dementia.MethodsThis is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer's disease. The patient took Aricept for the treatment of Alzheimer's disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018.ResultsThe patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons.ConclusionsThis finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer's disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer's disease.

Dataset Information

Lipids and brain inflammation in APOE4-associated dementia.

Purpose of review

Recent findings

Summary

Publications

Lipids and brain inflammation in APOE4-associated dementia.

Similar Datasets

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