The small HDL particle hypothesis of Alzheimer's disease

Ashley E. Martinez; Gali Weissberger; Zsuzsanna Kuklenyik; Xulei He; Cristiana Meuret; Trusha Parekh; Jon C. Rees; Bryan A. Parks; Michael S. Gardner; Sarah M. King; Timothy S. Collier; Michael G. Harrington; Melanie D. Sweeney; Xinhui Wang; Berislav V. Zlokovic; Elizabeth Joe; Daniel A. Nation; Lon S. Schneider; Helena C. Chui; John R. Barr; S. Duke Han; Ronald M. Krauss; Hussein N. Yassine

doi:10.1002/alz.12649

The small HDL particle hypothesis of Alzheimer's disease

Ashley E. Martinez, Gali Weissberger, Zsuzsanna Kuklenyik, Xulei He, Cristiana Meuret, Trusha Parekh, Jon C. Rees, Bryan A. Parks, Michael S. Gardner, Sarah M. King, Timothy S. Collier, Michael G. Harrington, Melanie D. Sweeney, Xinhui Wang, Berislav V. Zlokovic, Elizabeth Joe, Daniel A. Nation, Lon S. Schneider, Helena C. Chui, John R. BarrS. Duke Han, Ronald M. Krauss, Hussein N. Yassine

Department of Social & Health Sciences

Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

Abstract

We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

Original language	English
Pages (from-to)	391-404
Number of pages	14
Journal	Alzheimer's and Dementia
Volume	19
Issue number	2
Early online date	13 Apr 2022
DOIs	https://doi.org/10.1002/alz.12649
State	Published - Feb 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

APOE
HDL
cerebrospinal fluid
cognition
lipidomics
proteomics

All Science Journal Classification (ASJC) codes

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

Access to Document

10.1002/alz.12649

Cite this

Martinez, A. E., Weissberger, G., Kuklenyik, Z., He, X., Meuret, C., Parekh, T., Rees, J. C., Parks, B. A., Gardner, M. S., King, S. M., Collier, T. S., Harrington, M. G., Sweeney, M. D., Wang, X., Zlokovic, B. V., Joe, E., Nation, D. A., Schneider, L. S., Chui, H. C., ... Yassine, H. N. (2023). The small HDL particle hypothesis of Alzheimer's disease. Alzheimer's and Dementia, 19(2), 391-404. https://doi.org/10.1002/alz.12649

@article{4702212ddce14a129b68fef8183769b9,

title = "The small HDL particle hypothesis of Alzheimer's disease",

abstract = "We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.",

keywords = "APOE, HDL, cerebrospinal fluid, cognition, lipidomics, proteomics",

author = "Martinez, \{Ashley E.\} and Gali Weissberger and Zsuzsanna Kuklenyik and Xulei He and Cristiana Meuret and Trusha Parekh and Rees, \{Jon C.\} and Parks, \{Bryan A.\} and Gardner, \{Michael S.\} and King, \{Sarah M.\} and Collier, \{Timothy S.\} and Harrington, \{Michael G.\} and Sweeney, \{Melanie D.\} and Xinhui Wang and Zlokovic, \{Berislav V.\} and Elizabeth Joe and Nation, \{Daniel A.\} and Schneider, \{Lon S.\} and Chui, \{Helena C.\} and Barr, \{John R.\} and Han, \{S. Duke\} and Krauss, \{Ronald M.\} and Yassine, \{Hussein N.\}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = feb,

doi = "10.1002/alz.12649",

language = "الإنجليزيّة",

volume = "19",

pages = "391--404",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc.",

number = "2",

}

Martinez, AE, Weissberger, G, Kuklenyik, Z, He, X, Meuret, C, Parekh, T, Rees, JC, Parks, BA, Gardner, MS, King, SM, Collier, TS, Harrington, MG, Sweeney, MD, Wang, X, Zlokovic, BV, Joe, E, Nation, DA, Schneider, LS, Chui, HC, Barr, JR, Han, SD, Krauss, RM & Yassine, HN 2023, 'The small HDL particle hypothesis of Alzheimer's disease', Alzheimer's and Dementia, vol. 19, no. 2, pp. 391-404. https://doi.org/10.1002/alz.12649

TY - JOUR

T1 - The small HDL particle hypothesis of Alzheimer's disease

AU - Martinez, Ashley E.

AU - Weissberger, Gali

AU - Kuklenyik, Zsuzsanna

AU - He, Xulei

AU - Meuret, Cristiana

AU - Parekh, Trusha

AU - Rees, Jon C.

AU - Parks, Bryan A.

AU - Gardner, Michael S.

AU - King, Sarah M.

AU - Collier, Timothy S.

AU - Harrington, Michael G.

AU - Sweeney, Melanie D.

AU - Wang, Xinhui

AU - Zlokovic, Berislav V.

AU - Joe, Elizabeth

AU - Nation, Daniel A.

AU - Schneider, Lon S.

AU - Chui, Helena C.

AU - Barr, John R.

AU - Han, S. Duke

AU - Krauss, Ronald M.

AU - Yassine, Hussein N.

PY - 2023/2

Y1 - 2023/2

N2 - We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

AB - We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

KW - APOE

KW - HDL

KW - cerebrospinal fluid

KW - cognition

KW - lipidomics

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=85128104641&partnerID=8YFLogxK

U2 - 10.1002/alz.12649

DO - 10.1002/alz.12649

M3 - مقالة

C2 - 35416404

SN - 1552-5260

VL - 19

SP - 391

EP - 404

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 2

ER -

The small HDL particle hypothesis of Alzheimer's disease

Abstract

UN SDGs

Keywords

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this