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

OBJECTIVE: Accumulation of amyloid‐β is among the earliest changes in Alzheimer’s disease (AD). Amyloid‐β positron emission tomography (PET) and Aβ (42) 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 neu...

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Autores principales: 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, Bouwman, Femke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664271/
https://www.ncbi.nlm.nih.gov/pubmed/33080124
http://dx.doi.org/10.1002/acn3.51195
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author 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
Bouwman, Femke
author_facet 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
Bouwman, Femke
author_sort Reimand, Juhan
collection PubMed
description OBJECTIVE: Accumulation of amyloid‐β is among the earliest changes in Alzheimer’s disease (AD). Amyloid‐β positron emission tomography (PET) and Aβ (42) 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 (42) 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 (42) 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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spelling pubmed-76642712020-11-17 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 Bouwman, Femke Ann Clin Transl Neurol Research Articles OBJECTIVE: Accumulation of amyloid‐β is among the earliest changes in Alzheimer’s disease (AD). Amyloid‐β positron emission tomography (PET) and Aβ (42) 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 (42) 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 (42) 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. John Wiley and Sons Inc. 2020-10-20 /pmc/articles/PMC7664271/ /pubmed/33080124 http://dx.doi.org/10.1002/acn3.51195 Text en © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
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
Bouwman, Femke
Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
title Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
title_full Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
title_fullStr Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
title_full_unstemmed Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
title_short Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
title_sort amyloid‐β pet and csf in an autopsy‐confirmed cohort
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664271/
https://www.ncbi.nlm.nih.gov/pubmed/33080124
http://dx.doi.org/10.1002/acn3.51195
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