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

Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-beta (A beta) pathology. Objective: To compare the [C-11]PIB PET uptake in the patients with suspected iNPH to A beta and hyperphosphorylated-tau (HP tau) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) A beta, 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 A beta and HP tau in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [C-1(1)]PIB PET. A beta, total tau, and P tau(181) 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: [C-11]PIB uptake in the right frontal cortex (rho = 0.60, p < 0.01) and the combined neocortical [C-11]PIB uptake score (rho = 0.61, p < 0.01) were associated with a higher A beta load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [C-11]PIB uptake was also associated with the ventricular CSF A beta (rho = -0.58, p = 0.03). Conclusions: The findings show that [C-11]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 A beta pathology in the patients with iNPH might also warrant treatment with current AD drugs.