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Cited by 114Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchBarrier Structure and Function Studies

HDL from an Alzheimer's disease perspective

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Button, Emily B., Robert, Jérôme, Caffrey, Tara M., Fan, Jianjia, Zhao, Wenchen, Wellington, Cheryl L.·2019·Current Opinion in Lipidology
DOI 10.1097/mol.0000000000000604PMC PMC6530968
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Abstract

Purpose of review: We review current knowledge regarding HDL and Alzheimer's disease, focusing on HDL's vasoprotective functions and potential as a biomarker and therapeutic target for the vascular contributions of Alzheimer's disease. Recent findings: Many epidemiological studies have observed that circulating HDL levels associate with decreased Alzheimer's disease risk. However, it is now understood that the functions of HDL may be more informative than levels of HDL cholesterol (HDL-C). Animal model studies demonstrate that HDL protects against memory deficits, neuroinflammation, and cerebral amyloid angiopathy (CAA). In-vitro studies using state-of-the-art 3D models of the human blood–brain barrier (BBB) confirm that HDL reduces vascular Aβ accumulation and attenuates Aβ-induced endothelial inflammation. Although HDL-based therapeutics have not been tested in clinical trials for Alzheimer's disease , several HDL formulations are in advanced phase clinical trials for coronary artery disease and atherosclerosis and could be leveraged toward Alzheimer's disease . Summary: Evidence from human studies, animal models, and bioengineered arteries supports the hypothesis that HDL protects against cerebrovascular dysfunction in Alzheimer's disease. Assays of HDL functions relevant to Alzheimer's disease may be desirable biomarkers of cerebrovascular health. HDL-based therapeutics may also be of interest for Alzheimer's disease, using stand-alone or combination therapy approaches.

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  • Altered cholesterol, HDL and LDL metabolism, gene variants of APOA1, APOB, and APOE4, and decreased ApoA1 levels have been implicated in other neurologic disorders.

    “Altered cholesterol, HDL and LDL metabolism, gene variants of APOA1, APOB, and APOE4, and decreased ApoA1 levels have been implicated in other neurologic disorders [21–35].”

    From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [29]

    The Epidemiological Evidence section (page unavailable) links lower HDL-C and apoA-I levels with Alzheimer’s disease, and Figure 1 identifies APOE4 as a genetic risk factor. The cited paper does not establish the claimed involvement of APOA1 or APOB gene variants, or altered LDL metabolism, in neurologic disorders. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Button, E. B., Robert, J., Caffrey, T. M., Fan, J., Zhao, W., & Wellington, C. L.
Affiliations
University of British Columbia (CA)
Corresponding author
Wellington, Cheryl L.
ORCID
Venue
Current Opinion in Lipidology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-06
Volume
30
Issue
3
Pages
224-234
ISSN
  • 0957-9672 (ISSN-L)
  • 1473-6535
DOI
10.1097/mol.0000000000000604
PMC
PMC6530968
OpenAlex
W2926072937
Cited by
114
References
24
Citations by year
2026: 9 · 2025: 12 · 2024: 17 · 2023: 18 · 2022: 9 · 2021: 25 · 2020: 22 · 2019: 1 · 2018: 1
FWCI
1.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Lipidology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
HDL cholesterol, Alzheimer's disease, vascular protection, cerebrovascular dysfunction, biomarkers, therapeutic target, cerebral amyloid angiopathy, amyloid-beta, blood-brain barrier, endothelial inflammation, neuroinflammation, memory impairment
MeSH terms
Alzheimer Disease, Animals, Humans, Lipoproteins, HDL, Vascular Resistance, Comorbidity

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