Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers

Neurology. 2012 Jul 17;79(3):229-36. doi: 10.1212/WNL.0b013e31825fdf18. Epub 2012 Jun 13.


Objective: To investigate the particular pathology of the Arctic APP (APParc) early-onset familial Alzheimer disease (eoFAD) mutation for the first time in vivo with PET in comparison with other eoFAD mutations and sporadic Alzheimer disease (sAD).

Methods: We examined 2 APParc mutation carriers together with 5 noncarrier siblings cross-sectionally with (11)C-labeled Pittsburgh compound B (PiB) and (18)F-fluorodeoxyglucose (FDG) PET, as well as MRI, CSF biomarkers, and neuropsychological tests. Likewise, we examined 7 patients with sAD, 1 carrier of a presenilin 1 (PSEN1) mutation, 1 carrier of the Swedish APP (APPswe) mutation, and 7 healthy controls (HCs).

Results: Cortical PiB retention was very low in the APParc mutation carriers while cerebral glucose metabolism and CSF levels of Aβ(1-42), total and phosphorylated tau were clearly pathologic. This was in contrast to the PSEN1 and APPswe mutation carriers revealing high PiB retention in the cortex and the striatum in combination with abnormal glucose metabolism and CSF biomarkers, and the patients with sAD who showed typically high cortical PiB retention and pathologic CSF levels as well as decreased glucose metabolism when compared with HCs.

Conclusions: The lack of fibrillar β-amyloid (Aβ) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of Aβ(1-42) in CSF, that other forms of Aβ such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / genetics*
  • Aniline Compounds*
  • Atrophy
  • Biomarkers / cerebrospinal fluid*
  • Carbon Radioisotopes
  • Cognition / physiology
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Presenilin-1 / genetics
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • Thiazoles*
  • tau Proteins / cerebrospinal fluid


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Biomarkers
  • Carbon Radioisotopes
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • Radiopharmaceuticals
  • Thiazoles
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Fluorodeoxyglucose F18