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Cited by 80Alzheimer's disease research and treatmentsCholesterol and Lipid MetabolismCerebrospinal fluid and hydrocephalus

ABCA1‐Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer's Disease

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Yassine, Hussein N., Feng, Qingru, Chiang, Jiarong, Petrosspour, Larissa M., Fonteh, Alfred N., Chui, Helena C., Harrington, Michael G.·2016·Journal of the American Heart Association
DOI 10.1161/jaha.115.002886PMC PMC4802440
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Abstract

Background: Animal and human studies indicate that ABCA1‐mediated cholesterol transport is important in Alzheimer's disease (AD). We hypothesized that the efficiency of cerebrospinal fluid (CSF) to facilitate ABCA1‐mediated cholesterol efflux would be reduced in participants with mild cognitive impairment (MCI) or AD compared with cognitively healthy participants. Methods and Results: CSF was collected from a cross‐sectional study of cognitively healthy participants (n=47) and participants with MCI (n=35) or probable AD (n=26).The capacity of CSF to mediate cholesterol transport was assessed using a BHK cell line that can be induced to express the ABCA1 transporter. ABCA1‐mediated cholesterol efflux capacity was 30% less in participants with MCI or AD compared with cognitively healthy participants ( P <0.001 for both). Cholesterol efflux capacity correlated with CSF cholesterol content ( r =0.37, P <0.001). CSF phosphatidylcholine decreased in participants with MCI and AD compared with cognitively healthy participants (9% less in MCI and 27% less in AD compared with cognitively healthy participants, P =0.01) and correlated with CSF efflux capacity ( r =0.3, P =0.001). CSF sphingomyelin also correlated with the efflux capacity ( r =0.24, P =0.02). Concentrations of CSF apoA‐I and apoE did not significantly correlate with measures of efflux capacity. Conclusions: In people with MCI and AD, the capacity of CSF to facilitate ABCA1‐mediated cholesterol efflux is impaired. This lesser cholesterol efflux in MCI supports a pathophysiological role for ABCA1‐mediated cholesterol transport in early neurodegeneration.

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Authors
Yassine, H. N., Feng, Q., Chiang, J., Petrosspour, L. M., Fonteh, A. N., Chui, H. C., & Harrington, M. G.
Affiliations
  • University of Southern California (US)
  • Huntington Medical Research Institutes (US)
Corresponding author
Yassine, Hussein N.
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-02-23
Volume
5
Issue
2
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.115.002886
PMC
PMC4802440
OpenAlex
W2284826199
Cited by
80
References
8
Citations by year
2026: 3 · 2025: 5 · 2024: 11 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 10 · 2019: 10 · 2018: 4 · 2017: 5 · 2016: 3
FWCI
5.91
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Washington
  • National Institute on Aging (P50AG005142)
  • National Heart, Lung, and Blood Institute (K23HL107389)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
ABCA1, cholesterol efflux, cerebrospinal fluid, mild cognitive impairment, Alzheimer's disease, cholesterol transport, phosphatidylcholine, sphingomyelin, apolipoprotein A-I, apolipoprotein E, early neurodegeneration
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Animals, Biological Transport, Cell Line, Cholesterol, Cross-Sectional Studies, Female, Cricetinae, Humans, Male, Phosphatidylcholines, Transfection, Biomarkers, Down-Regulation, Case-Control Studies, Cognitive Dysfunction, ATP Binding Cassette Transporter 1

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