Association of lipocalin-type prostaglandin D synthase with disproportionately enlarged subarachnoid-space in idiopathic normal pressure hydrocephalus

Fluids and Barriers of the CNS

Masatsune Ishikawa⁴  Koichi Iwasaki⁵  Sadayuki Matsumoto²  Yoshihiro Urade¹  Mitsuhito Mase⁶  Akihiko Ozaki⁸  Kengo Uemura⁷  Naoto Jingami⁹  Hiroki Toda⁵  Nanae Nagata¹  Namiko Nishida³ 

[1] International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan;Department of Neurology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka 530-8480, Japan;Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan;Department of neurosurgery and normal pressure hydrocephalus center, Rakuwakai Otowa hospital, Kyoto 607-8062, Japan;Department of Neurosurgery, Tazuke Kofukai Foundation, Medical Research Institute and Kitano Hospital, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan;Department of Neurosurgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8602, Japan;Ishiki Hospital, Kagoshima 890-0005, Japan;Department of Neurology, Saiseikai Nakatsu Hospital, Osaka 530-0012, Japan;Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan

关键词: DESH;    White matter damage;    T-tau;    L-PGDS;    CSF biomarker;    Frontal lobe dysfunction;    Idiopathic normal pressure hydrocephalus;   

Others  :  813284
DOI  :  10.1186/2045-8118-11-9

 received in 2014-01-10, accepted in 2014-04-07,  发布年份 2014

【 摘 要 】

Background

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable cause of dementia, gait disturbance, and urinary incontinence in elderly patients with ventriculomegaly. Its unique morphological feature, called disproportionately enlarged subarachnoid-space hydrocephalus (DESH), may also be a diagnostic feature. Lipocalin-type prostaglandin D synthase (L-PGDS) is a major cerebrospinal fluid (CSF) protein produced by arachnoid cells, and its concentration in the CSF is reportedly decreased in iNPH. L-PGDS acts as a prostaglandin D2-producing enzyme and behaves as a chaperone to prevent the neurotoxic aggregation of amyloid beta (Aβ) implicated in Alzheimer’s disease, a major comorbidity of iNPH. The aim of this study was to confirm the L-PGDS decrease in DESH-type iNPH and to clarify its relationship with clinico-radiological features or other CSF biomarkers.

Methods

We evaluated 22 patients (age: 76.4 ± 4.4 y; males: 10, females: 12) referred for ventriculomegaly without CSF pathway obstruction, and conducted a CSF tap test to determine the surgical indication. CSF concentrations of L-PGDS, Aβ42, Aβ40, and total tau (t-tau) protein were determined using enzyme-linked immunosorbent assays. Clinical symptoms were evaluated by the iNPH grading scale, mini-mental state examination, frontal assessment battery (FAB), and timed up and go test. The extent of DESH was approximated by the callosal angle, and the severity of parenchymal damage was evaluated by the age-related white matter change (ARWMC) score.

Results

L-PGDS and t-tau levels in CSF were significantly decreased in DESH patients compared to non-DESH patients (p = 0.013 and p = 0.003, respectively). L-PGDS and t-tau showed a significant positive correlation (Spearman r = 0.753, p < 0.001). Among the clinico-radiological profiles, L-PGDS levels correlated positively with age (Spearman r = 0.602, p = 0.004), callosal angle (Spearman r = 0.592, p = 0.004), and ARWMC scores (Spearman r = 0.652, p = 0.001), but were negatively correlated with FAB scores (Spearman r = 0.641, p = 0.004).

Conclusions

Our data support the diagnostic value of L-PGDS as a CSF biomarker for iNPH and suggest a possible interaction between L-PGDS and tau protein. In addition, L-PGDS might work as a surrogate marker for DESH features, white matter damage, and frontal lobe dysfunction.

【 授权许可】

   
2014 Nishida et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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