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Idiopathic Normal Pressure Hydrocephalus has a Different Cerebrospinal Fluid Biomarker Profile from Alzheimer's Disease

Article type: Research Article

Authors: Jingami, Naotoa; b | Asada-Utsugi, Megumia; b | Uemura, Kengoa; b; c | Noto, Rioa | Takahashi, Makiod; e | Ozaki, Akihikod; f | Kihara, Takeshig | Kageyama, Takashih | Takahashi, Ryosukea | Shimohama, Shuni; * | Kinoshita, Ayaeb

Affiliations: [a] Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan | [b] Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan | [c] Department of Neurology, Ishiki Hospital, Kagoshima, Japan | [d] Department of Neurology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan | [e] Department of Neurology, Osaka Redcross Hospital, Osaka, Japan | [f] Department of Neurology, Kitano Hospital, Osaka, Japan | [g] Department of Neurology, Misasagi Hospital, Kyoto, Japan | [h] Department of Neurology, Tenri Yorozu Hospital, Nara, Japan | [i] Department of Neurology, Sapporo Medical University, Sapporo, Japan

Correspondence: [*] Correspondence to: Shun Shimohama, Department of Neurology, School of Medicine, Sapporo Medical University, Address: South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. Tel.: +81 11 611 2111; Fax: +81 11 622 7668; E-mail: [email protected].

Keywords: Alzheimer's disease, amyloid-β, analysis of covariate, idiopathic normal pressure hydrocephalus, leucine-rich α-2-glycoprotein, Mini-Mental State Examination, tap test, tau phosphorylated at threonine 181, total tau

DOI: 10.3233/JAD-142622

Journal: Journal of Alzheimer's Disease, vol. 45, no. 1, pp. 109-115, 2015

Accepted 12 November 2014
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Published: 3 March 2015
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Abstract

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is sometimes complicated by concomitant Alzheimer's disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-β (Aβ) 42 and 40, and leucine-rich α-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and Aβ42 in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although Aβ42/40 ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of Aβ40 and Aβ42 correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD.

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