Phosphorylated tau/amyloid beta 1-42 ratio in ventricular cerebrospinal fluid reflects outcome in idiopathic normal pressure hydrocephalus

Fluids and Barriers of the CNS

Roy H Hamilton⁴  John Q Trojanowski⁵  M Sean Grady²  Leslie M Shaw⁵  Christopher M Clark⁶  Steven E Arnold⁶  Eric M Jackson²  Anica Law³  Sharon X Xie¹  Edward B Lee⁵  Sunil Patel⁴ 

[1] Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA;Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA;University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA;Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA;Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA 19104, USA;Penn Memory Center, University of Pennsylvania, Philadelphia, PA 19104, USA

关键词: Cerebrospinal fluid;    Amyloid beta 1-42;    Tau;    Ventriculoperitoneal shunting;    Normal pressure hydrocephalus;    Alzheimer's disease;   

Others  :  807344
DOI  :  10.1186/2045-8118-9-7

 received in 2011-11-23, accepted in 2012-03-23,  发布年份 2012

【 摘 要 】

Background

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of dementia and gait disturbance that is typically treated by operative placement of a ventriculoperitoneal shunt. The outcome from shunting is variable, and some evidence suggests that the presence of comorbid Alzheimer's disease (AD) may impact shunt outcome. Evidence also suggests that AD biomarkers in cerebrospinal fluid (CSF) may predict the presence of AD. The aim of this study was to investigate the relationship between the phosphorylated tau/amyloid beta 1-42 (ptau/Aβ1-42) ratio in ventricular CSF and shunt outcome in patients with iNPH.

Methods

We conducted a prospective trial with a cohort of 39 patients with suspected iNPH. Patients were clinically and psychometrically assessed prior to and approximately 4 months after ventriculoperitoneal shunting. Lumbar and ventricular CSF obtained intraoperatively, and tissue from intraoperative cortical biopsies were analyzed for AD biomarkers. Outcome measures included performance on clinical symptom scales, supplementary gait measures, and standard psychometric tests. We investigated relationships between the ptau/Aβ1-42 ratio in ventricular CSF and cortical AD pathology, initial clinical features, shunt outcome, and lumbar CSF ptau/Aβ1-42 ratios in the patients in our cohort.

Results

We found that high ptau/Aβ1-42 ratios in ventricular CSF correlated with the presence of cortical AD pathology. At baseline, iNPH patients with ratio values most suggestive of AD presented with better gait performance but poorer cognitive performance. Patients with high ptau/Aβ1-42 ratios also showed a less robust response to shunting on both gait and cognitive measures. Finally, in a subset of 18 patients who also underwent lumbar puncture, ventricular CSF ratios were significantly correlated with lumbar CSF ratios.

Conclusions

Levels of AD biomarkers in CSF correlate with the presence of cortical AD pathology and predict aspects of clinical presentation in iNPH. Moreover, preliminary evidence suggests that CSF biomarkers of AD may prove useful for stratifying shunt prognosis in patients being evaluated and treated for this condition.

【 授权许可】

   
2012 Patel et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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