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

J Alzheimers Dis. 2019;67(4):1343-1351. doi: 10.3233/JAD-180645.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy / methods
  • Carbon Radioisotopes / pharmacology*
  • Female
  • Finland
  • Follow-Up Studies
  • Frontal Lobe* / diagnostic imaging
  • Frontal Lobe* / metabolism
  • Frontal Lobe* / pathology
  • Humans
  • Hydrocephalus, Normal Pressure* / diagnosis
  • Hydrocephalus, Normal Pressure* / metabolism
  • Hydrocephalus, Normal Pressure* / pathology
  • Hydrocephalus, Normal Pressure* / psychology
  • Male
  • Mental Status and Dementia Tests
  • Positron-Emission Tomography / methods*
  • Reproducibility of Results
  • Ventricular Pressure
  • Ventriculoperitoneal Shunt / methods
  • tau Proteins / metabolism


  • Carbon Radioisotopes
  • Carbon-11
  • tau Proteins