Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus

Abstract

ObjectiveCerebrospinal fluid (CSF) shunting can improve symptoms of elderly patients' idiopathic normal pressure hydrocephalus (iNPH). However, adjunctive means for confirming the diagnosis remain unavailable. We have previously reported the specific increase of leucine-rich alpha-2-glycoprotein (LRG) in iNPH CSF, and the present study investigates its potential clinical applications.MethodsWe performed CSF tap test (TT) on 90 patients (mean age 73.4 years) and shunting in 52 patients (mean age 73.5 years), evaluating symptom improvement and higher cerebral functions—mini-mental state examination (MMSE) and Frontal Assessment Battery (FAB) before and 12 months after shunting. LRG and tau protein concentrations in TT CSF were simultaneously measured using enzyme-linked immunosorbent assay. We then compared the predictive value of these concentrations with TT results regarding successful shunting outcomes.ResultsPositive combinations of TT and LRG concentrations of 67 ng/ml or higher, gave 81.6% sensitivity and 78.6% specificity. Therefore we used LRG (67 ng/ml) and tau (200 pg/ml) cut-off values, dividing patients into four groups. In group A (LRG ≥ 67 ng/ml and tau < 200 pg/ml) 31 of 34 patients (91.2%) had a positive TT and all operated 22 patients were shunt responders. Dementia MMSE and FAB scores in them increased from a baseline of 22.05(SE ± 0.96) to 25.65 (±0.85) and 11.38 (±0.68) to 13.08 (±0.57) respectively. In group B, (LRG ≥ 67 ng/ml and tau ≥ 200 pg/ml), the mean MMSE score increased from 17.62 (±2.03) to 21.62 (±1.96), and the FAB decreased slightly from 9.25 (±1.15) to 10.5 (±1.59), without improvement beyond the range of dementia. In group C, (LRG < 67 ng/ml, tau < 200 pg/ml), the mean MMSE score improved from 22.06 (±1.25) to 24.29 (±1.23) and the FAB score improved slightly from 12.0 (±0.72) to 12.87 (±0.72). Finally, in group D, (LRG < 67 ng/ml, tau ≥ 200 pg/ml), there was almost no improvement in MMSE scoreConclusionsA combination of positive TT and biomarkers quantification such as LRG and tau protein, can reliably predict shunting outcome in iNPH patients.

Leucine-Rich α2-Glycoprotein Is a Novel Biomarker of Neurodegenerative Disease in Human Cerebrospinal Fluid and Causes Neurodegeneration in Mouse Cerebral Cortex

“…This study was conducted over a period of 6 years between January 2006 and September 2012 on consecutive, unselected admissions to our program for 100 patients with clinically suspected iNPH (63 men, 37 women; mean age 75.8 ± 6.7 years) [17,18]. In addition, 26 elderly individuals (13 men, 13 women; mean age, 68.3 ± 9.8 years) without subjective cognitive impairment or known brain disease, with MMSE scores >25 and who consented to lumbar puncture at the Juntendo University Hospital were included as non-demented NCs.…”

LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway

“…It was then characterized to be a glycoprotein containing 312 amino acid residues of which 66 are leucine (Takahashi et al, 1985). Studies have shown that the level of LRG1 is elevated in the sera and the tumor tissues of patients with non-small-cell lung cancer (Nakajima et al, 2011;O'Donnell et al, 2002). Similarly, the level of LRG1 has been found to be elevated in the sera of colorectal cancer patients, and is closely correlated with tumor progression (Ladd et al, 2012).…”

Resection of Multiple Neurinomas of the Cauda Equina Improves Normal Pressure Hydrocephalus

“…In addition, some neurotoxic molecules, which tumors produce, may increase or impair neurotransmission. Leucine-rich alpha-2-glycoprotein was elevated in the CSF of iNPH patients [14]. sNPH cases may also have neurotoxic substances produced by tumors.…”