Amyloid-ß PET and CSF in an autopsy-confirmed cohort.

ABSTRACT

OBJECTIVE: Accumulation of amyloid-ß is among the earliest changes in Alzheimer's disease (AD). Amyloid-ß positron emission tomography (PET) and Aß42 in cerebrospinal fluid (CSF) both assess amyloid-ß pathology in-vivo, but 10-20% of cases show discordant (CSF+/PET- or CSF-/PET+) results. The neuropathological correspondence with amyloid-ß CSF/PET discordance is unknown. METHODS: We included 21 patients from our tertiary memory clinic who had undergone both CSF Aß42 analysis and amyloid-ß PET, and had neuropathological data available. Amyloid-ß 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-ß PET was positive in all A3, C2, and C3 cases and in one of the two A2 cases. CSF Aß42 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-ß CSF/PET discordance. Furthermore, amyloid-ß 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-ß biomarker results.