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Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus.
J Alzheimers Dis. 2021; 83(1):179-190.JA

Abstract

BACKGROUND

The amyloid-β oligomers, consisting of 10-20 monomers (AβO10-20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer's disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood.

OBJECTIVE

We hypothesized that cerebrospinal fluid (CSF) AβO10-20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10-20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role.

METHODS

We evaluated two iNPH cohorts: "evaluation" (cohort-1) with 32 patients and "validation" (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson's disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10-20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1's clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10-20 levels at baseline, 1 and 3 years after shunting.

RESULTS

Cohort-1 had higher CSF AβO10-20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10-20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10-20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10-20 decrease showed better cognitive outcome than those without.

CONCLUSION

AβO10-20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10-20 can be an applicable diagnostic and prognostic biomarker.

Authors+Show Affiliations

Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo Tokyo Koto Geriatric Medical Centre, Shinsuna Koto-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurology, Mihara Memorial Hospital, Ota-cho, Isesaki-shi, Gunma, Japan.Department of Neurology, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Medical Technology Innovation Center, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo Tokyo Koto Geriatric Medical Centre, Shinsuna Koto-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan. Department of Neurosurgery, Kugayama Hospital, Kita-Karasuyama, Setagaya-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Molecular Genetics, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.Department of Neurosurgery, Juntendo University, Hongo Bunkyo-ku, Tokyo, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34275898

Citation

Kawamura, Kaito, et al. "Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients With Idiopathic Normal Pressure Hydrocephalus." Journal of Alzheimer's Disease : JAD, vol. 83, no. 1, 2021, pp. 179-190.
Kawamura K, Miyajima M, Nakajima M, et al. Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2021;83(1):179-190.
Kawamura, K., Miyajima, M., Nakajima, M., Kanai, M., Motoi, Y., Nojiri, S., Akiba, C., Ogino, I., Xu, H., Kamohara, C., Yamada, S., Karagiozov, K., Ikeuchi, T., Kondo, A., & Arai, H. (2021). Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus. Journal of Alzheimer's Disease : JAD, 83(1), 179-190. https://doi.org/10.3233/JAD-210226
Kawamura K, et al. Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients With Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2021;83(1):179-190. PubMed PMID: 34275898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus. AU - Kawamura,Kaito, AU - Miyajima,Masakazu, AU - Nakajima,Madoka, AU - Kanai,Mitsuyasu, AU - Motoi,Yumiko, AU - Nojiri,Shuko, AU - Akiba,Chihiro, AU - Ogino,Ikuko, AU - Xu,Hanbing, AU - Kamohara,Chihiro, AU - Yamada,Shinya, AU - Karagiozov,Kostadin, AU - Ikeuchi,Takeshi, AU - Kondo,Akihide, AU - Arai,Hajime, PY - 2021/7/20/pubmed PY - 2021/11/27/medline PY - 2021/7/19/entrez KW - Amyloid-β peptides KW - biomarkers KW - cerebrospinal fluid KW - neurodegenerative diseases KW - normal pressure hydrocephalus SP - 179 EP - 190 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 83 IS - 1 N2 - BACKGROUND: The amyloid-β oligomers, consisting of 10-20 monomers (AβO10-20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer's disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. OBJECTIVE: We hypothesized that cerebrospinal fluid (CSF) AβO10-20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10-20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. METHODS: We evaluated two iNPH cohorts: "evaluation" (cohort-1) with 32 patients and "validation" (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson's disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10-20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1's clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10-20 levels at baseline, 1 and 3 years after shunting. RESULTS: Cohort-1 had higher CSF AβO10-20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10-20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10-20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10-20 decrease showed better cognitive outcome than those without. CONCLUSION: AβO10-20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10-20 can be an applicable diagnostic and prognostic biomarker. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/34275898/Cerebrospinal_Fluid_Amyloid_β_Oligomer_Levels_in_Patients_with_Idiopathic_Normal_Pressure_Hydrocephalus_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-210226 DB - PRIME DP - Unbound Medicine ER -