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

Reimand, Juhan ; Boon, Baayla D.C. ; Collij, Lyduine E. ; Teunissen, Charlotte E. ; Rozemuller, Annemieke J.M. ; van Berckel, Bart N.M. ; Scheltens, Philip ; Ossenkoppele, Rik LU and Bouwman, Femke (2020) In Annals of Clinical and Translational Neurology 7(11). p.2150-2160
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of Clinical and Translational Neurology
volume
7
issue
11
pages
11 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85092711232
  • pmid:33080124
ISSN
2328-9503
DOI
10.1002/acn3.51195
language
English
LU publication?
yes
id
37bec1ff-2e71-460d-88a5-2ca8b9fb4d79
date added to LUP
2020-11-12 11:14:47
date last changed
2024-06-27 01:16:22
@article{37bec1ff-2e71-460d-88a5-2ca8b9fb4d79,
  abstract     = {{<p>Objective: Accumulation of amyloid-β is among the earliest changes in Alzheimer’s disease (AD). Amyloid-β positron emission tomography (PET) and Aβ<sub>42</sub> 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 Aβ<sub>42</sub> 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 Aβ<sub>42</sub> 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.</p>}},
  author       = {{Reimand, Juhan and Boon, Baayla D.C. and Collij, Lyduine E. and Teunissen, Charlotte E. and Rozemuller, Annemieke J.M. and van Berckel, Bart N.M. and Scheltens, Philip and Ossenkoppele, Rik and Bouwman, Femke}},
  issn         = {{2328-9503}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2150--2160}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Annals of Clinical and Translational Neurology}},
  title        = {{Amyloid-β PET and CSF in an autopsy-confirmed cohort}},
  url          = {{http://dx.doi.org/10.1002/acn3.51195}},
  doi          = {{10.1002/acn3.51195}},
  volume       = {{7}},
  year         = {{2020}},
}