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Title: Plasma high-density lipoprotein cargo is altered in Alzheimer's disease and is associated with regional brain volume.
Austin Authors: Pedrini, Steve;Doecke, James D;Hone, Eugene;Wang, Penghao;Thota, Rohith;Bush, Ashley I;Rowe, Christopher C ;Doré, Vincent ;Villemagne, Victor L ;Ames, David;Rainey-Smith, Stephanie;Verdile, Giuseppe;Sohrabi, Hamid R;Raida, Manfred R;Taddei, Kevin;Gandy, Sam;Masters, Colin L ;Chatterjee, Pratishtha;Martins, Ralph N
Affiliation: University of Melbourne Academic unit for Psychiatry of Old Age, St George's Hospital, Kew, Victoria, Australia..
Australian E-Health Research Centre, CSIRO, Brisbane, Queensland, Australia..
School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia..
CRC for Mental Health, Melbourne, Victoria, Australia..
College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Western Australia, Australia..
Faculty of Medicine, Health and Human Sciences, Department of Biomedical Sciences, Macquarie University, Sydney, New South Wales, Australia..
The Florey Institute of Neuroscience and Mental Health
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia..
Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, Western Australia, Australia..
Curtin Medical School, Curtin University, Bentley, Western Australia, Australia..
Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia..
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia..
National Ageing Research Institute, Parkville, Victoria, Australia..
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA..
Life Science Institute, Singapore Lipidomics Incubator, National University of Singapore, Singapore City, Singapore..
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA..
Issue Date: 30-Jul-2022 2022
Publication information: Journal of Neurochemistry 2022; 163(1): 53-67
Abstract: Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) in stable healthy control (HC), healthy controls who will convert to MCI/AD (HC-Conv) and AD patients (AD). Compared to HC we observed an increased cholesterol/ApoA-I ratio in AD and HC-Conv, as well as an increased ApoD/ApoA-I ratio and a decreased ApoA-II/ApoA-I ratio in AD. Higher cholesterol/ApoA-I ratio was also associated with lower cortical grey matter volume and higher ventricular volume, while higher ApoA-II/ApoA-I and ApoJ/ApoA-I ratios were associated with greater cortical grey matter volume (and for ApoA-II also with greater hippocampal volume) and smaller ventricular volume. Additionally, in a clinical status-independent manner, the ApoE/ApoA-I ratio was significantly lower in APOE ε4 carriers and lowest in APOE ε4 homozygous. Together, these data indicate that in AD patients the composition of HDL is altered, which may affect HDL functionality, and such changes are associated with altered regional brain volumetric data.
DOI: 10.1111/jnc.15681
Journal: Journal of Neurochemistry
PubMed URL: 36000528
PubMed URL:
Type: Journal Article
Subjects: Alzheimer's disease
Appears in Collections:Journal articles

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