Amyloid-β PET and CSF in an autopsy-confirmed cohort

Ann Clin Transl Neurol. 2020 Nov;7(11):2150-2160. doi: 10.1002/acn3.51195. Epub 2020 Oct 20.


Objective: Accumulation of amyloid-β is among the earliest changes in Alzheimer's disease (AD). Amyloid-β positron emission tomography (PET) and Aβ42 in cerebrospinal fluid (CSF) both assess amyloid-β pathology in-vivo, but 10-20% of cases show discordant (CSF+/PET- or CSF-/PET+) results. The neuropathological correspondence with amyloid-β CSF/PET discordance is unknown.

Methods: We included 21 patients from our tertiary memory clinic who had undergone both CSF Aβ42 analysis and amyloid-β PET, and had neuropathological data available. Amyloid-β PET and CSF results were compared with neuropathological ABC scores (comprising of Thal (A), Braak (B), and CERAD (C) stage, all ranging from 0 [low] to 3 [high]) and neuropathological diagnosis.

Results: Neuropathological diagnosis was AD in 11 (52%) patients. Amyloid-β PET was positive in all A3, C2, and C3 cases and in one of the two A2 cases. CSF Aβ42 was positive in 92% of ≥A2 and 90% of ≥C2 cases. PET and CSF were discordant in three of 21 (14%) cases: CSF+/PET- in a patient with granulomatosis with polyangiitis (A0B0C0), CSF+/PET- in a patient with FTLD-TDP type B (A2B1C1), and CSF-/PET+ in a patient with AD (A3B3C3). Two CSF+/PET+ cases had a non-AD neuropathological diagnosis, that is FTLD-TDP type E (A3B1C1) and adult-onset leukoencephalopathy with axonal spheroids (A1B1C0).

Interpretation: Our study demonstrates neuropathological underpinnings of amyloid-β CSF/PET discordance. Furthermore, amyloid-β biomarker positivity on both PET and CSF did not invariably result in an AD diagnosis at autopsy, illustrating the importance of considering relevant comorbidities when evaluating amyloid-β biomarker results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / metabolism*
  • Autopsy
  • Biomarkers / metabolism
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Positron-Emission Tomography*


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)

Grants and funding

This work was funded by Alzheimer Nederland and Stichting VUmc grant .