[¹¹C]PIB PET Is Associated with the Brain Biopsy Amyloid-β Load in Subjects Examined for Normal Pressure Hydrocephalus

Article type: Research Article

Authors: Rinne, Juha O.^{a; b; *} | Suotunen, Timo^a | Rummukainen, Jaana^c | Herukka, Sanna-Kaisa^{d; e} | Nerg, Ossi^d | Koivisto, Anne M.^{d; e} | Rauramaa, Tuomas^{c; f} | Någren, Kjell^g | Hiltunen, Mikko^h | Alafuzoff, Irinaⁱ | Rinne, Jaakko^j | Jääskeläinen, Juha E.^{k; l} | Soininen, Hilkka^e | Leinonen, Ville^{k; l; m}

Affiliations: [a] Turku PET Centre, University of Turku, Turku, Finland | [b] Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland | [c] Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland | [d] Neurology of NeuroCenter, Kuopio University Hospital, Kuopio, Finland | [e] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland | [f] Institute of Clinical Medicine, Pathology, University of Eastern Finland, Kuopio, Finland | [g] Department of Nuclear Medicine, PET and Cyclotron Unit, Odense University Hospital, Odense, Denmark | [h] Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland | [i] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden | [j] Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland | [k] Institute of Clinical Medicine, Neurosurgery, University of Eastern Finland, Kuopio, Finland | [l] Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland | [m] Unit of Clinical Neuroscience, Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland

Correspondence: [*] Correspondence to: Juha Rinne, Turku PET Centre, University of Turku, Kiinamyllynkatu 4 - 8, 20520 Turku, Finland. Tel.: +358-2-3131866; E-mail: [email protected].

Abstract: Background:Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology. Objective:To compare the [11C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer’s disease (AD). Methods:Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [11C]PIB PET. Aβ, total tau, and Pτ181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3–1). Results:[11C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [11C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [11C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= –0.58, p = 0.03). Conclusions:The findings show that [11C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.

Keywords: Amyloid, brain biopsy, cerebrospinal fluid, normal pressure hydrocephalus, positron emission tomography

DOI: 10.3233/JAD-180645

Journal: Journal of Alzheimer's Disease, vol. 67, no. 4, pp. 1343-1351, 2019