title: Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer's disease.
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.
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Jingami
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Asada-Utsugi
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Neurology, Ishiki Hospital, Kagoshima, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Rio
authors.initials: R
authors.lastname: Noto
authors.affiliation: Department of Neurology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan Department of Neurology, Osaka Redcross Hospital, Osaka, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan Department of Neurology, Kitano Hospital, Osaka, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ozaki
authors.affiliation: Department of Neurology, Misasagi Hospital, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kihara
authors.affiliation: Department of Neurology, Tenri Yorozu Hospital, Nara, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kageyama
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.affiliation: Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000704:Analysis of Variance; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001927:Brain Diseases / Q000134:cerebrospinal fluid; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D000511:alpha-Macroglobulins / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D000511:alpha-Macroglobulins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Mini-Mental State Examination; amyloid-β; analysis of covariate; idiopathic normal pressure hydrocephalus; leucine-rich α-2-glycoprotein; tap test; tau phosphorylated at threonine 181; total tau