Increased PCSK9 cerebrospinal fluid concentrations in Alzheimer's disease

Francesca Zimetti, Paolo Caffarra, Nicoletta Ronda, Elda Favari, Maria Pia Adorni, Ilaria Zanotti, Franco Bernini, F. Barocco, Marco Spallazzi, Daniela Galimberti, Chiara Ricci, M. Ruscica, Alberto Corsini, Nicola Ferri

Research output: Contribution to journalArticlepeer-review


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 Aβ42 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 ϵ4 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.

Original languageEnglish
Pages (from-to)315-320
Number of pages6
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 2017


  • Alzheimer's disease
  • apolipoprotein E4
  • cerebrospinal fluid
  • cholesterol
  • human
  • proprotein convertase subtilisin kexin 9

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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