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

Akiba, Chihiro; Nakajima, Madoka; Miyajima, Masakazu; Ogino, Ikuko; Motoi, Yumiko; Kawamura, Kaito; Adachi, Satoshi; Kondo, Akihide; Sugano, Hidenori; Tokuda, Takahiko; Irie, Kazuhiro; Arai, Hajime

doi:10.3233/jad-180059

Cited by 21 publications

(14 citation statements)

References 47 publications

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“…Nonetheless, a significant difference in the amount of toxic conformer between AD/MCI and control groups was not observed, possibly because of the small number of samples. Indeed, Akiba et al, [87] reported significantly high levels of the toxic conformer in AD patients using our ELISA kit. They also suggested that the ratio of toxic conformer to total A42 in patients with idiopathic normal pressure hydrocephalus (iNPH) was significantly higher than control groups.…”

Section: Development Of An Anti-toxic-turn Antibody 24b3 and Its Apmentioning

confidence: 67%

New diagnostic method for Alzheimer’s disease based on the toxic conformation theory of amyloid β

Irie

2020

Bioscience, Biotechnology, and Biochemistry

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Recent investigations suggest that soluble oligomeric amyloid  (A) species may be involved in early onset of Alzheimer's disease (AD). Using systematic proline replacement, solid-state NMR, and ESR, we identified a toxic turn at position 22 and 23 of A42, the most potent neurotoxic A species. Through radicalization, the toxic turn can induce formation of the C-terminal hydrophobic core to obtain putative A42 dimers and trimers. Synthesized dimer and trimer models showed that the C-terminal hydrophobic core plays a critical role in formation of high molecular weight oligomers with neurotoxicity. Accordingly, an anti-toxic turn antibody (24B3) that selectively recognizes a toxic dimer model of E22P-A42 was developed. Sandwich enzyme-linked immunosorbent assay with 24B3 and 82E1 detected a significantly higher ratio of A42 with a toxic turn to total A42 in cerebrospinal fluid of AD patients compared with controls, suggesting that 24B3 could be useful for early onset of AD diagnosis.

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Section: Development Of An Anti-toxic-turn Antibody 24b3 and Its Apmentioning

confidence: 67%

New diagnostic method for Alzheimer’s disease based on the toxic conformation theory of amyloid β

Irie

2020

Bioscience, Biotechnology, and Biochemistry

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“…For example, stroke affects functional prognosis, cancer affects life prognosis, Alzheimer's disease affects cognitive function, and Parkinson’s disease affects motor function. 208 , 274 , 280) All of these can notably affect the long-term outcomes of a shunt intervention. It is therefore good to predict the coexistence of comorbidities, such as Alzheimer's disease, using biomarkers before surgery.…”

Section: Chapter 5 Postoperative Management and Prognosismentioning

confidence: 99%

Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus

Nakajima

Yamada

Miyajima

et al. 2021

Neurol. Med. Chir.(Tokyo)

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Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.

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“…For postoperative follow-up, we adjusted the valve pressure and monitored proper shunt function with CSF withdrawal via valve reservoir puncture as previously reported. (7,16) If shunt malfunction was detected, the patient underwent shunt revision immediately.…”

Section: Csf Analysismentioning

confidence: 99%

Cerebrospinal fluid levels of amyloid-beta oligomers in patients with idiopathic normal pressure hydrocephalus are elevated before shunt surgery but decrease afterward

Kawamura

Miyajima

Nakajima

et al. 2020

Preprint

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Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.

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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

Cited by 21 publications

References 47 publications

New diagnostic method for Alzheimer’s disease based on the toxic conformation theory of amyloid β

New diagnostic method for Alzheimer’s disease based on the toxic conformation theory of amyloid β

Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus

Cerebrospinal fluid levels of amyloid-beta oligomers in patients with idiopathic normal pressure hydrocephalus are elevated before shunt surgery but decrease afterward

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