Change of Amyloid-β 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus.

Content Provider	Europe PMC
Author	Akiba, Chihiro Nakajima, Madoka Miyajima, Masakazu Ogino, Ikuko Motoi, Yumiko Kawamura, Kaito Adachi, Satoshi Kondo, Akihide Sugano, Hidenori Tokuda, Takahiko Irie, Kazuhiro Arai, Hajime
Copyright Year	2018
Abstract	Background:Alzheimer’s disease (AD) pathology in idiopathic normal pressure hydrocephalus (iNPH) contributes to poor shunt responses. Amyloid-β 1– 42 (Aβ42) toxic conformer was recently identified with features of rapid oligomerization, strong neurotoxicity and synaptotoxicity.Objective:This observational study points to Aβ42 toxic conformer as a biomarker for AD pathology and for poor postoperative prognosis in patients with iNPH.Methods:The first cohort consisted of patients with AD (n = 17) and iNPH (n = 17), and cognitively normal individuals (CN, n = 12). The second cohort, consisted of 51 patients with iNPH, was divided into two groups according to phosphorylated Tau (pTau) level (low- and high-pTau groups); the low-pTau group was further subdivided according to one-year postoperative change in Aβ42 toxic conformer ratio (%) [Aβ42 toxic conformer/Aβ42×100] (decreased- and increased-conformer subgroups). Enzyme-linked immunosorbent assay was used to measure pTau, Aβ42, and Aβ42 toxic conformer in cerebrospinal fluid. Outcomes were evaluated using neuropsychological tests one- and two-years postoperatively.Results:In the first cohort, Aβ42 toxic conformer ratio in the iNPH group (10.8%) was significantly higher than that in the CN group (6.3%) and significantly lower than that in the AD group (17.2%). In the second cohort, the high-pTau group showed cognitive decline two-years postoperatively compared to baseline. However, the low-pTau group showed favorable outcomes one-year postoperatively; furthermore, the increased-conformer subgroup showed cognitive decline two-years postoperatively while the decreased-conformer subgroup maintained the improvement.Conclusions:Change in Aβ42 toxic conformer ratio predicts long-term cognitive outcome in iNPH, even in the low-pTau group.
ISSN	13872877
Journal	Journal of Alzheimer's Disease
Volume Number	63
PubMed Central reference number	PMC6004932
Issue Number	3
PubMed reference number	29710721
e-ISSN	18758908
DOI	10.3233/JAD-180059
Language	English
Publisher	IOS Press
Publisher Date	2018-01-01
Publisher Place	Amsterdam, The Netherlands
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 – IOS Press and the authors. All rights reserved
Subject Keyword	Alzheimer’s disease amyloid-β 1-42 amyloid clearance cerebrospinal-fluid shunting cognitive function idiopathic normal pressure hydrocephalus oligomer phosphorylated tau toxic conformer
Content Type	Text
Resource Type	Article
Subject	Neuroscience Clinical Psychology Psychiatry and Mental Health Geriatrics and Gerontology