TY - JOUR
T1 - Alzheimer's disease: Elevated pigment epithelium-derived factor in the cerebrospinal fluid is mostly of systemic origin
AU - Lang, Veronika
AU - Zille, Marietta
AU - Infante-Duarte, Carmen
AU - Jarius, Sven
AU - Jahn, Holger
AU - Paul, Friedemann
AU - Ruprecht, Klemens
AU - Pina, Ana Luisa
N1 - Publisher Copyright:
© 2017
PY - 2017/4/15
Y1 - 2017/4/15
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Cerebrospinal fluid
KW - Meningitis
KW - Multiple sclerosis
KW - Pseudotumor cerebri
UR - http://www.scopus.com/inward/record.url?scp=85010302947&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2017.01.051
DO - 10.1016/j.jns.2017.01.051
M3 - Article
VL - 375
SP - 123
EP - 128
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510x
ER -