Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus

Miyajima, Masakazu; Nakajima, Madoka; Ogino, Ikuko; Miyata, Haruko; Motoi, Yumiko; Arai, Heii

doi:10.1111/j.1468-1331.2012.03781.x

Cited by 56 publications

(43 citation statements)

References 34 publications

(44 reference statements)

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“…41 Specifically, the cutoff value for predicting cognitive outcomes in Miyajima et al’s study 41 was 198ng/ml, which is considerably lower than our value of 514ng/ml for sAPPα. In a related study, Pyykko et al 42 concluded that increases in APP isoforms were independent of neuroinflammation mechanisms in patients with idiopathic normal pressure hydrocephalus.…”

Section: Discussioncontrasting

confidence: 71%

Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule

et al. 2016

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Background Intraventricular hemorrhage (IVH) is the most frequent, severe neurological complication of prematurity and is associated with post-hemorrhagic hydrocephalus (PHH) in up to half of cases. PHH requires lifelong neurosurgical care and is associated with significant cognitive and psychomotor disability. Cerebrospinal fluid (CSF) biomarkers may provide both diagnostic information for PHH and novel insights into its pathophysiology. Objective To explore the diagnostic ability of candidate CSF biomarkers for PHH. Methods Concentrations of amyloid precursor protein (APP), soluble APPα, sAPPβ, NCAM-1, L1CAM, tau, phosphorylated tau, and total CSF protein (TP) were measured in lumbar CSF from neonates in six groups: (a) no known neurological disease (n=33); (b) IVH Grades I-II (n=13); (c) IVH Grades III-IV (n=12); (d) PHH (n=12); (e) ventricular enlargement without hydrocephalus (n=10); and (f) hypoxic ischemic encephalopathy (n=13). CSF protein levels were compared using analysis of variance, and logistic regression was performed to examine the predictive ability of each marker for PHH. Results Lumbar CSF levels of APP, sAPPα, L1CAM, and TP were selectively increased in PHH compared to all other conditions (all p<0.0001). The sensitivity, specificity, and odds ratios of candidate CSF biomarkers for PHH were determined for APP, sAPPα, and L1CAM; cutpoints of 699, 514, and 113 ng/ml yielded odds ratios for PHH of 80.0, 200.0, and 68.75, respectively. Conclusion Lumbar CSF APP, sAPPα, L1CAM, and TP were selectively increased in PHH. These proteins, and sAPPα in particular, hold promise as biomarkers of PHH and provide novel insight into PHH-associated neural injury and repair.

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Section: Discussioncontrasting

confidence: 71%

Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule

et al. 2016

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“…A total of 413 patients with iNPH, 186 patients with AD, and 147 healthy controls were included in this meta-analysis. 2 studies were performed in the United States [21, 22], 2 in Japan [23, 24], 2 in Sweden [12, 25], 1 in Greece [13], 1 in Finland [26], 1 in South Korea [27] and 1 in Italy [28]. These studies were published between 2007 and 2015.…”

Section: Resultsmentioning

confidence: 99%

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

Chen

Liu

Zhang

et al. 2017

Fluids Barriers CNS

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ObjectivesThe purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls.MethodsStudies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016. The standardized mean difference (SMD) and 95% confidence interval (CI), comparing CSF Aβ42, t-tau, and p-tau levels between iNPH, AD and healthy controls, were calculated using random-effects models. Subgroup analyses were created according to ethnicity (Caucasian or Asian) and CSF type (lumbar or ventricular), and the publication bias was estimated using Egger’s test and the Begg’s test.ResultsA total of 10 studies including 413 patients with iNPH, 186 patients with AD and 147 healthy controls were included in this systematic review and meta-analysis. The concentrations of CSF t-tau, and p-tau were significantly lower in iNPH patients compared to AD (SMD = −1.26, 95% CI −1.95 to −0.57, P = 0.0004; SMD = −1.54, 95% CI −2.34 to −0.74, P = 0.0002, respectively) and lower than healthy controls (SMD = −0.80, 95% CI −1.50 to −0.09, P = 0.03; SMD = −1.12, 95% CI −1.38 to −0.86, P < 0.00001, respectively). Patients with iNPH had significantly lower Aβ42 levels compared with controls (SMD = −1.14, 95% CI −1.74 to −0.55, P = 0.0002), and slightly higher Aβ42 levels compared with AD patients (SMD = 0.32, 95% CI 0.00–0.63, P = 0.05). Subgroup analyses showed that the outcomes may have been influenced by ethnicity and CSF source. Compared to AD, overall sensitivity in differentiating iNPH was 0.813 (95% CI 0.636–0.928) for Aβ42, 0.828 (95% CI 0.732–0.900) for t-tau, 0.943 (95% CI 0.871–0.981) for p-tau. Relative to AD, overall specificity in differentiating iNPH was 0.506 (95% CI 0.393–0.619) for Aβ42, 0.842 (95% CI 0.756–0.907) for t-tau, 0.851 (95% CI 0.767–0.914) for p-tau.ConclusionThe results of our meta-analysis suggest that iNPH may be associated with significantly reduced levels of CSF Aβ42, t-tau and p-tau compared to the healthy normal state. Compared to AD, both t-tau and p-tau were significantly decreased in iNPH, but CSF Aβ42 was slightly increased. Prospective studies are needed to further assess the clinical utility of these and other CSF biomarkers in assisting in the diagnosis of iNPH and differentiating it from AD and other neurodegenerative disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12987-017-0062-5) contains supplementary material, which is available to authorized users.

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“…We previously reported that measurement of sAPPα in the CSF is useful for differential diagnosis of iNPH [19]. CSF amyloid precursor protein (sAPP, sAPPαand sAPPβ) levels in iNPH patients are significantly lower than in normal control subjects of all age groups.…”

Section: Discussionmentioning

confidence: 98%

Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus

Nakajima

Miyajima

Ogino

et al. 2015

Journal of the Neurological Sciences

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The prognosis of cognitive improvement after cerebrospinal fluid (CSF) shunting in idiopathic normal pressure hydrocephalus (iNPH) remains uncertain, with no reports on CSF biomarkers related to long-term cognitive prognosis. We performed a preliminary study of CSF biomarker protein levels for cognitive outcome prognostication of two-year outcomes after shunt treated iNPH in 36 patients (13 women) with a median age of 75years (IQR 69-78). CSF biomarkers included soluble amyloid precursor proteins (sAPP, sAPPα, sAPPβ), amyloid β (Aβ)1-38, Aβ1-42 and phosphorylated tau (p-tau), lipocalin-type prostaglandin D synthase (L-PGDS)/β-trace, and cystatin C. The results clearly showed that p-tau levels (sensitivity of 71.4%, specificity of 77.8%, cut-off value of 22.0pg/mL), Aβ1-38/Aβ1-42 ratio (77.8%, 81%, 3.58), and the Aβ1-42/p-tau ratio (76%, 72.7%, 14.6) in preoperative CSF have the potential to determine postoperative prognosis. Improved cognition may be associated with the improvement in CSF circulation after LPS, which likely induces cystatin C and L-PGDS and switches synthesis from Aβ1-42 to Aβ1-38.

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Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus

Abstract: Our results show that sAPPα is a suitable biomarker for the diagnosis and prognosis of iNPH.

Cited by 56 publications

References 34 publications

Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule

Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus

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