Background: Alzheimer's disease (AD) has been associated with dysregulation of brain cholesterol trafficking and abnormal production of apolipoprotein E isoform 4 (apoE4). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein present in serum and cerebrospinal fluid (CSF) degrading the low-density lipoprotein receptor (LDLr) and other apoE-binding receptors involved in neuron cholesterol uptake. The role of PCSK9 in AD is controversial. Objective: We compared PCSK9 levels in CSF of AD patients and non-AD controls and looked at correlations with CSF total apoE and apoE4. Methods: CSF from AD (n = 30) and from age and sex-matched non-AD patients (n = 30) was collected by lumbar puncture for routine diagnosis. CSF PCSK9, total apoE, and apoE4 levels were measured by ELISA. AD patients showed the typical CSF neurobiomarker pattern (decreased A beta(42) and increased tau and phospho-tau) and impaired cognitive performances, as indicated by the scores of the Mini-Mental State Examination test. Results: PCSK9 levels in CSF were higher in AD than in non-AD subjects (+1.45 fold; p = 0.0049). CSF total apoE concentrations did not differ between the two groups, while apoE4 levels were higher in AD subjects (+3.34 fold; p = 0.0068). Considering all samples, a significant positive correlation was found between PCSK9 and apoE4 (r = 0.4409; p = 0.0006). PCSK9 levels were higher in APOE epsilon 4 carriers, reaching statistical significance in the AD group (+1.45 fold; p = 0.0454). Conclusion: These results report for the first time an alteration of CSF PCSK9 levels in AD and suggest a pathophysiological link between PCSK9, apoE4, and AD.
Increased PCSK9 Cerebrospinal Fluid Concentrations in Alzheimer's Disease / F. Zimetti, P. Caffarra, N. Ronda, E. Favari, M.P. Adorni, I. Zanotti, F. Bernini, F. Barocco, M. Spallazzi, D. Galimberti, C. Ricci, M. Ruscica, A. Corsini, N. Ferri. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 55:1(2017 Jan), pp. 315-320.
|Titolo:||Increased PCSK9 Cerebrospinal Fluid Concentrations in Alzheimer's Disease|
CORSINI, ALBERTO (Penultimo)
FERRI, NICOLA (Ultimo)
|Parole Chiave:||Alzheimer's disease; apolipoprotein E4; cerebrospinal fluid; cholesterol; human; proprotein convertase subtilisin kexin 9|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/04 - Patologia Generale
|Progetto:||Investigating the role of pro-protein convertase subtilisin/kexin type 9 (PCSK9) released from smooth muscle cells on atherogenesis|
|Data di pubblicazione:||gen-2017|
|Data ahead of print / Data di stampa:||gen-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3233/JAD-160411|
|Appare nelle tipologie:||01 - Articolo su periodico|