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- Pyykkö, Okko T, et al.
(författare)
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Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e91974-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brain biopsy. Quantified Ab load in the brain biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.
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| 2. |
- Leinonen, Ville, et al.
(författare)
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Cortical Brain Biopsy in Long-Term Prognostication of 468 Patients with Possible Normal Pressure Hydrocephalus
- 2012
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 10:1-4, s. 166-169
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Tidskriftsartikel (refereegranskat)abstract
- Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer's disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of brain biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical brain biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0-17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.
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