O Nerg

Publications (2)12 Total impact

• Article: Positron emission tomography with [(18) F]flutemetamol and [(11) C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.

  V Leinonen, J O Rinne, K A Virtanen, O Eskola, J Rummukainen, J Huttunen, M von Und Zu Fraunberg, O Nerg, A M Koivisto, J Rinne, J E Jääskeläinen, C Buckley, A Smith, P A Jones, P Sherwin, G Farrar, R McLain, M Kailajärvi, K Heurling, I D Grachev
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  ABSTRACT: BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [(18) F]flutemetamol PET. Seven of these patients also underwent [(11) C] Pittsburgh compound B (PiB) PET. [(18) F]Flutemetamol and [(11) C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. RESULTS: [(18) F]Flutemetamol and [(11) C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [(11) C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003). CONCLUSIONS: [(18) F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.
  European Journal of Neurology 02/2013; · 3.69 Impact Factor
• Article: CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.

  T T Seppälä, O Nerg, A M Koivisto, J Rummukainen, L Puli, H Zetterberg, O T Pyykkö, S Helisalmi, I Alafuzoff, M Hiltunen, J E Jääskeläinen, J Rinne, H Soininen, V Leinonen, S K Herukka
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  ABSTRACT: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels. Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.
  Neurology 04/2012; 78(20):1568-75. · 8.31 Impact Factor