Elevated CSF LRG and Decreased Alzheimer's Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Aleksi Vanninen; Madoka Nakajima; Masakazu Miyajima; Tuomas Rauramaa; Merja Kokki; Tadeusz Musialowicz; Petra M Mäkinen; Sanna-Kaisa Herukka; Anne M Koivisto; Juha E Jääskeläinen; Mikko Hiltunen; Ville Leinonen

doi:10.3390/jcm10051105

Elevated CSF LRG and Decreased Alzheimer's Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

J Clin Med. 2021 Mar 6;10(5):1105. doi: 10.3390/jcm10051105.

Authors

Aleksi Vanninen^{1

2}, Madoka Nakajima³, Masakazu Miyajima⁴, Tuomas Rauramaa^{5

6}, Merja Kokki^{7

8}, Tadeusz Musialowicz^{7

8}, Petra M Mäkinen⁹, Sanna-Kaisa Herukka^{10

11}, Anne M Koivisto^{10

11

12

13}, Juha E Jääskeläinen^{1

2}, Mikko Hiltunen⁹, Ville Leinonen^{1

2}

Affiliations

¹ Department of Neurosurgery, Kuopio University Hospital, FI-70029 Kuopio, Finland.
² Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
³ Department of Neurosurgery, Juntendo University School of Medicine, Tokyo 113-8342, Japan.
⁴ Department of Neurosurgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo 136-0075, Japan.
⁵ Department of Pathology, Kuopio University Hospital, FI-70029 Kuopio, Finland.
⁶ Pathology, Institute of Clinical Medicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
⁷ Department of Anaesthesia and Intensive Care Medicine, Kuopio University Hospital, FI-70029 Kuopio, Finland.
⁸ School of Medicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
⁹ Institute of Biomedicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
¹⁰ Department of Neurology, Kuopio University Hospital, FI-70029 Kuopio, Finland.
¹¹ Neurology, Institute of Clinical Medicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
¹² Department of Neurosciences, University of Helsinki, FI-00014 Helsinki, Finland.
¹³ Department of Geriatrics, Helsinki University Hospital, FI-00014 Helsinki, Finland.

Abstract

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer's disease (AD) pathology among the iNPH patients. CSF LRG, Aβ_1-42, P-tau₁₈₁, and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p < 0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., Aβ_1-42, T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls (<0.001). Our findings support that the LRG levels in the CSF are potentially useful for the diagnostics of iNPH, independent of the brain AD pathology, but contrary to previous findings, not for predicting the shunt response. Our findings also suggest a need for specific reference values of the CSF AD biomarkers for the diagnostics of comorbid AD pathology in the iNPH patients.

Keywords: Alzheimer’s disease; biopsy; brain; cerebrospinal fluid; hydrocephalus; normal pressure.

Abstract

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