Alzheimer's disease: Elevated pigment epithelium-derived factor in the cerebrospinal fluid is mostly of systemic origin.
Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19). We established CSF/serum quotient diagrams to determine the fraction of intrathecally synthesized PEDF in CSF. We found that PEDF is significantly increased in CSF of patients with AD, FTD, and bacterial meningitis. Remarkably, PEDF concentrations were also significantly elevated in serum of patients with AD. CSF/serum quotient diagrams demonstrated that elevated PEDF concentrations in CSF of patients with AD are mostly due to elevated PEDF concentrations in serum. These findings underscore the importance of relating concentrations of proteins in CSF to their respective concentrations in serum to avoid erroneous interpretations of increased protein concentrations in lumbar CSF.
Department of Neurosurgery, Experimental Neurosurgery, Charité - Universitätsmedizin, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin, Berlin, Germany.
Veronika
V
Lang
Department of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin, Berlin, Germany; Department of Neurology and Neuroscience, The Burke Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY, USA.
Marietta
M
Zille
Experimental Neuroimmunology Research Group, Institute for Medical Immunology, Charité - Universitätsmedizin, Berlin, Germany.
Carmen
C
Infante-Duarte
Molecular Neuroimmunology Group, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
Sven
S
Jarius
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Holger
H
Jahn
NeuroCure Clinical Research Center, Charité - Universitätsmedizin, Berlin, Germany; Department of Neurology, Charité - Universitätsmedizin, Berlin, Germany; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin, Germany.
Friedemann
F
Paul
Department of Neurology, Charité - Universitätsmedizin, Berlin, Germany.
Klemens
K
Ruprecht
Department of Neurosurgery, Experimental Neurosurgery, Charité - Universitätsmedizin, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin, Berlin, Germany. Electronic address: ana-luisa.pina@charite.de.
Ana Luisa
AL
Pina
D000328:Adult; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood / Q000134:cerebrospinal fluid*; D015843:Serpins / Q000097:blood / Q000134:cerebrospinal fluid*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
Alzheimer's disease; Cerebrospinal fluid; Meningitis; Multiple sclerosis; Pseudotumor cerebri