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using Human Progranulin ELISA Kits (Adipogen Inc., Korea). P4-121 NEUROPROTECTIVE EFFECT OF SERUM URIC
Other biomarkers included routine AD markers (Ab1-42, hTau and ACID ON ALZHEIMER’S DISEASE IS MEDIATED
pTau181P, INNOTEST, Fujirebio Europe, Belgium) and NF-light BY BRAIN METABOLISM CHANGE
(UmanDiagnostics, IBL International GmbH, Germany). Results: Byoung Seok Ye1, Woo Seok Ha2, Jae Jung Lee1, Yoonju Lee3,
FTLD-GRN patients had the lowest serum and CSF progranulin Phil Hyu Lee1, Young H. Sohn1, 1Yonsei University College of Medicine,
levels of all groups, which determined the significances when Seoul, South Korea; 2Yonsei University College of Medicine, Seoul,
comparing FTLD-TDP and FTLD-tau groups (p<0.05) and when Republic of Korea; 3Yonsei University College of Medicine, Severance
comparing FTLD, AD and controls (p<0.02). Progranulin levels Hospital, Seoul, Republic of Korea. Contact e-mail: romel79@gmail.com
in CSF and serum were significantly correlated in all FTLD sub- Background: Previous studies suggested that higher level of serum
groups except C9orf72 repeat expansions carriers. CSF levels of uric acid (UA) has a protective effect on cognitive decline in non-
markers for neurodegeneration (hTau and NF-light) were highest demented subjects. We evaluated the relationship between serum
in FTLD-GRN patients as compared to other FTLD-subgroups UA, brain metabolism, and longitudinal cognitive decline in pa-
(Table 1). A cox hazard regression analysis (corrected for age at tients with mild cognitive impairment (MCI) using Alzheimer’s
onset) in another cohort of dementia patients without motor neuron disease Neuroimaging Initiative database. Methods: In 682 patients
disease, showed a mean disease duration of 5.6y62.6y in GRN car- with MCI, serum UA and CSF amyloid beta (Abeta) were measured
riers (n¼40) and 8.2y65.0y in C9orf72 carriers (n¼30) (p¼0.051) at baseline. According to the baseline CSF Abeta (cut-off value, 192
(Figure 1). Conclusions: Our results confirm that CSF and serum pg/mL) and gender, MCI patients were categorized into female/am-
progranulin levels can reliably identify GRN mutation carriers in yloid-positive, female/amyloid-negative, male/amyloid-positive,
a dementia cohort. The increased CSF levels of tau and NF-light and male/amyloid-negative subgroups. Brain metabolism in five re-
chain in GRN mutation carrying FTLD patients suggest more neu- gions of interests (left/right angular gyrus, left/right inferior tempo-
rodegeneration in this subgroup. GRN carriers indeed have a shorter ral gyrus, and bilateral cingulate gyrus) were evaluated using 18F-
disease duration than C9orf72 carriers. 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
Table 1
Mean 6 S.E. values of progranulin, total tau and neurofilament light chain
evaluated using linear mixed effect models controlling for possible
levels in CSF of FTLD- subgroups. Statistical differences with FTLD-GRN confounders. Results: Higher serum UA level was associated with
(p<0.05) are marked with an asterisk (*). slower decline in brain metabolism in female group (every ROIs,
p < 0.001), but not in male group. Higher level of UA was associ-
FTLD-GRN FTLD-C9orf72 FTLD-tau
ated with slower cognitive decline in female/amyloid-positive
progranulin (ng/ml) 1.93 6 0.35 2.98 6 0.30* 3.66 6 0.34* group (p ¼ 0.04 for MMSE and p ¼ 0.03 for ADAS-cog), but not
total tau (pg/ml) 411.7 6 42.6 289.8 6 34.2* 331.8 6 57.9 in other three subgroups. The significant effect of serum UA on
neurofilament light 7305 6 848 3548 6 472* 3906 6 1082* cognitive decline in female/amyloid-positive subgroup disappeared
chain (pg/ml) 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.