1. Amyloid‐β PET and CSF in an autopsy‐confirmed cohort
- Author
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Philip Scheltens, Bart N.M. van Berckel, Charlotte E. Teunissen, Annemieke J.M. Rozemuller, Femke H. Bouwman, Lyduine E. Collij, Baayla D.C. Boon, Rik Ossenkoppele, Juhan Reimand, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pathology, Radiology and nuclear medicine, and Laboratory Medicine
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Neurology ,Autopsy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Cohort Studies ,Leukoencephalopathy ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Alzheimer Disease ,mental disorders ,Humans ,Medicine ,Stage (cooking) ,RC346-429 ,Research Articles ,Aged ,Amyloid beta-Peptides ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,Middle Aged ,medicine.disease ,Peptide Fragments ,030104 developmental biology ,Positron emission tomography ,Positron-Emission Tomography ,Biomarker (medicine) ,Female ,Neurology (clinical) ,Neurology. Diseases of the nervous system ,business ,Granulomatosis with polyangiitis ,Biomarkers ,030217 neurology & neurosurgery ,Research Article ,RC321-571 - Abstract
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.
- Published
- 2020
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