Abstract
HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes toward the neurons that rely on this supply for their functions. We evaluated whether cell cholesterol efflux capacity of CSF (CSF-CEC) is impaired in Alzheimer's disease (AD) by analyzing AD (n = 37) patients, non-AD dementia (non-AD DEM; n = 16) patients, and control subjects (n = 39). As expected, AD patients showed reduced CSF Aβ 1-42, increased total and phosphorylated tau, and a higher frequency of the apo?4 genotype. ABCA1- and ABCG1-mediated CSF-CEC was markedly reduced in AD (-73% and -33%, respectively) but not in non-AD DEM patients, in which a reduced passive diffusion CEC (-40%) was observed. Non-AD DEM patients displayed lower CSF apoE concentrations (-24%) compared with controls, while apoA-I levels were similar among groups. No differences in CSF-CEC were found by stratifying subjects for apoϵ4 status. ABCG1 CSF-CEC positively correlated with Aβ 1-42 (r = 0.305, P = 0.025), while ABCA1 CSF-CEC inversely correlated with total and phosphorylated tau (r = -0.348, P = 0.018 and r = -0.294, P = 0.048, respectively). The CSF-CEC impairment and the correlation with the neurobiochemical markers suggest a pathophysiological link between CSF HDL-like particle dysfunction and neurodegeneration in AD.- Marchi, C., M. P. Adorni, P. Caffarra, N. Ronda, M. Spallazzi, F. Barocco, D. Galimberti, F. Bernini, and F. Zimetti. ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease. J. Lipid Res. 2019. 60: 1449-1456.
| Original language | English |
|---|---|
| Pages (from-to) | 1449-1456 |
| Number of pages | 8 |
| Journal | Journal of Lipid Research |
| Volume | 60 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- Apolipoprotein A-I
- Apolipoprotein E
- Apolipoprotein E4
- Apolipoproteins
- ATP-binding cassette A1
- ATP-binding cassette G1
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology
Cite this
ABCA1- And ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease. / Marchi, Cinzia; Adorni, Maria Pia; Caffarra, Paolo; Ronda, Nicoletta; Spallazzi, Marco; Barocco, Federica; Galimberti, Daniela; Bernini, Franco; Zimetti, Francesca.
In: Journal of Lipid Research, Vol. 60, No. 8, 01.01.2019, p. 1449-1456.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ABCA1- And ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease
AU - Marchi, Cinzia
AU - Adorni, Maria Pia
AU - Caffarra, Paolo
AU - Ronda, Nicoletta
AU - Spallazzi, Marco
AU - Barocco, Federica
AU - Galimberti, Daniela
AU - Bernini, Franco
AU - Zimetti, Francesca
PY - 2019/1/1
Y1 - 2019/1/1
N2 - HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes toward the neurons that rely on this supply for their functions. We evaluated whether cell cholesterol efflux capacity of CSF (CSF-CEC) is impaired in Alzheimer's disease (AD) by analyzing AD (n = 37) patients, non-AD dementia (non-AD DEM; n = 16) patients, and control subjects (n = 39). As expected, AD patients showed reduced CSF Aβ 1-42, increased total and phosphorylated tau, and a higher frequency of the apo?4 genotype. ABCA1- and ABCG1-mediated CSF-CEC was markedly reduced in AD (-73% and -33%, respectively) but not in non-AD DEM patients, in which a reduced passive diffusion CEC (-40%) was observed. Non-AD DEM patients displayed lower CSF apoE concentrations (-24%) compared with controls, while apoA-I levels were similar among groups. No differences in CSF-CEC were found by stratifying subjects for apoϵ4 status. ABCG1 CSF-CEC positively correlated with Aβ 1-42 (r = 0.305, P = 0.025), while ABCA1 CSF-CEC inversely correlated with total and phosphorylated tau (r = -0.348, P = 0.018 and r = -0.294, P = 0.048, respectively). The CSF-CEC impairment and the correlation with the neurobiochemical markers suggest a pathophysiological link between CSF HDL-like particle dysfunction and neurodegeneration in AD.- Marchi, C., M. P. Adorni, P. Caffarra, N. Ronda, M. Spallazzi, F. Barocco, D. Galimberti, F. Bernini, and F. Zimetti. ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease. J. Lipid Res. 2019. 60: 1449-1456.
AB - HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes toward the neurons that rely on this supply for their functions. We evaluated whether cell cholesterol efflux capacity of CSF (CSF-CEC) is impaired in Alzheimer's disease (AD) by analyzing AD (n = 37) patients, non-AD dementia (non-AD DEM; n = 16) patients, and control subjects (n = 39). As expected, AD patients showed reduced CSF Aβ 1-42, increased total and phosphorylated tau, and a higher frequency of the apo?4 genotype. ABCA1- and ABCG1-mediated CSF-CEC was markedly reduced in AD (-73% and -33%, respectively) but not in non-AD DEM patients, in which a reduced passive diffusion CEC (-40%) was observed. Non-AD DEM patients displayed lower CSF apoE concentrations (-24%) compared with controls, while apoA-I levels were similar among groups. No differences in CSF-CEC were found by stratifying subjects for apoϵ4 status. ABCG1 CSF-CEC positively correlated with Aβ 1-42 (r = 0.305, P = 0.025), while ABCA1 CSF-CEC inversely correlated with total and phosphorylated tau (r = -0.348, P = 0.018 and r = -0.294, P = 0.048, respectively). The CSF-CEC impairment and the correlation with the neurobiochemical markers suggest a pathophysiological link between CSF HDL-like particle dysfunction and neurodegeneration in AD.- Marchi, C., M. P. Adorni, P. Caffarra, N. Ronda, M. Spallazzi, F. Barocco, D. Galimberti, F. Bernini, and F. Zimetti. ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease. J. Lipid Res. 2019. 60: 1449-1456.
KW - Apolipoprotein A-I
KW - Apolipoprotein E
KW - Apolipoprotein E4
KW - Apolipoproteins
KW - ATP-binding cassette A1
KW - ATP-binding cassette G1
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U2 - 10.1194/jlr.P091033
DO - 10.1194/jlr.P091033
M3 - Article
VL - 60
SP - 1449
EP - 1456
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 8
ER -