Poster Presentations: Wednesday, July 27, 2016
using Human Progranulin ELISA Kits (Adipogen Inc., Korea).
Other biomarkers included routine AD markers (Ab1-42, hTau and
pTau181P, INNOTEST, Fujirebio Europe, Belgium) and NF-light
(UmanDiagnostics, IBL International GmbH, Germany). Results:
FTLD-GRN patients had the lowest serum and CSF progranulin
levels of all groups, which determined the significances when
comparing FTLD-TDP and FTLD-tau groups (p<0.05) and when
comparing FTLD, AD and controls (p<0.02). Progranulin levels
in CSF and serum were significantly correlated in all FTLD sub-
groups except C9orf72 repeat expansions carriers. CSF levels of
markers for neurodegeneration (hTau and NF-light) were highest
in FTLD-GRN patients as compared to other FTLD-subgroups
(Table 1). A cox hazard regression analysis (corrected for age at
onset) in another cohort of dementia patients without motor neuron
disease, showed a mean disease duration of 5.6y62.6y in GRN car-
riers (n¼40) and 8.2y65.0y in C9orf72 carriers (n¼30) (p¼0.051)
(Figure 1). Conclusions: Our results confirm that CSF and serum
progranulin levels can reliably identify GRN mutation carriers in
a dementia cohort. The increased CSF levels of tau and NF-light
chain in GRN mutation carrying FTLD patients suggest more neu-
rodegeneration in this subgroup. GRN carriers indeed have a shorter
disease duration than C9orf72 carriers.
Table 1
Mean 6 S.E. values of progranulin, total tau and neurofilament light chain
levels in CSF of FTLD- subgroups. Statistical differences with FTLD-GRN
(p<0.05) are marked with an asterisk (*).
FTLD-GRN FTLD-C9orf72 FTLD-tau
progranulin (ng/ml) 1.93 6 0.35 2.98 6 0.30* 3.66 6 0.34*
total tau (pg/ml) 411.7 6 42.6 289.8 6 34.2* 331.8 6 57.9
neurofilament light 7305 6 848 3548 6 472* 3906 6 1082*
chain (pg/ml)
Figure 1. Cox hazard regression analysis of disease duration in GRN car-
riers (n¼59) versus C9orf72 carriers (n¼53) with pure dementia
(p¼0.051), corrected for age at onset. Numbers include deceased patients
(GRN: n¼40; C9orf72: n¼30) and living patients censored at time of last
evaluation (GRN: n¼19; C9orf72: n¼23).
P1059
P4-121 NEUROPROTECTIVE EFFECT OF SERUM URIC
ACID ON ALZHEIMER’S DISEASE IS MEDIATED
BY BRAIN METABOLISM CHANGE
Byoung Seok Ye1, Woo Seok Ha2, Jae Jung Lee1, Yoonju Lee3,
Phil Hyu Lee1, Young H. Sohn1, 1Yonsei University College of Medicine,
Seoul, South Korea; 2Yonsei University College of Medicine, Seoul,
Republic of Korea; 3Yonsei University College of Medicine, Severance
Hospital, Seoul, Republic of Korea. Contact e-mail: romel79@gmail.com
Background: Previous studies suggested that higher level of serum
uric acid (UA) has a protective effect on cognitive decline in non-
demented subjects. We evaluated the relationship between serum
UA, brain metabolism, and longitudinal cognitive decline in pa-
tients with mild cognitive impairment (MCI) using Alzheimer’s
disease Neuroimaging Initiative database. Methods: In 682 patients
with MCI, serum UA and CSF amyloid beta (Abeta) were measured
at baseline. According to the baseline CSF Abeta (cut-off value, 192
pg/mL) and gender, MCI patients were categorized into female/am-
yloid-positive, female/amyloid-negative, male/amyloid-positive,
and male/amyloid-negative subgroups. Brain metabolism in five re-
gions of interests (left/right angular gyrus, left/right inferior tempo-
ral gyrus, and bilateral cingulate gyrus) were evaluated using 18F-
fludeoxyglucose positron emission tomography (FDG-PET).
Cognitive changes were assessed using Mini-Mental Status Exam-
ination (MMSE) and Alzheimer’s Disease Assessment Scale-
cognitive subscale (ADAS-cog). The effect of baseline serum UA
on longitudinal changes in brain metabolism and cognition was
evaluated using linear mixed effect models controlling for possible
confounders. Results: Higher serum UA level was associated with
slower decline in brain metabolism in female group (every ROIs,
p < 0.001), but not in male group. Higher level of UA was associ-
ated with slower cognitive decline in female/amyloid-positive
group (p ¼ 0.04 for MMSE and p ¼ 0.03 for ADAS-cog), but not
in other three subgroups. The significant effect of serum UA on
cognitive decline in female/amyloid-positive subgroup disappeared
when brain metabolism in the left angular gyrus was further
controlled for. Conclusions: Higher serum UA had female-specific
protective effects on longitudinal cognitive decline in MCI
patients, which were mediated by the protective effect on brain
metabolism.
P4-122 PREVALENCE OF VASCULAR RISK FACTORS IN
DIFFERENT STAGES OF PRODROMAL
ALZHEIMER’S DISEASE AND ITS INFLUENCE ON
COGNITIVE DECLINE
Isabelle Bos1, Stephanie J. B. Vos1, Lutz Fr€olich2, Johannes Kornhuber3,
Jens Wiltfang4, Wolfgang Maier5, Oliver Peters6, Eckhart R€uther7,
Sebastiaan Engelborghs8,9, Ellis Niemantsverdriet9, Ellen Elisa De Roeck9,
Magda Tsolaki10, Yvonne Freund-Levi11, Peter Johannsen12,
Rik Vandenberghe13, Alberto Lleo14, Daniel Alcolea14,
Giovanni B. Frisoni15,16, Samantha Galluzzi16, Flavio Nobili17,
Silvia Morbelli18, Alexander Drzezga19, Mira Didic20, Bart N. M. van
Berckel21, Eric Salmon22,23, Christine Bastin24, Solene Dauby22,
Isabel Santana25, In^es Baldeiras25, Alexandre Mendonça26, Dina Silva26,
Anders Wallin27, Arto Nordlund27, Nadia Foskett28, Preciosa Coloma29,
Myriam Alexander30, Angelika Wientzek-Fleischmann31, Alejo Nevado-
Holgado32, Usha Gungabissoon33, Gerald P. Novak34,
Mark Forrest Gordon35,  Asa K. Wallin36, Harald Hampel37,
Hilkka Soininen38, Philip Scheltens39, Frans R. J. Verhey1,
Pieter Jelle Visser21,40, 1Maastricht University, Maastricht, Netherlands;
2
Central Institute of Mental Health, University of Heidelberg, Mannheim,
Germany; 3Friedrich-Alexander University Erlangen-N€urnberg, Erlangen,
Germany; 4University Medical Center Goettingen,