Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-β 42/40 positivityopen access
- Authors
- Pyun, Jung-Min; Park, Young Ho; Youn, Young Chul; Kang, Min Ju; Shim, Kyu Hwan; Jang, Jae-Won; You, Jihwan; Nho, Kwangsik; Kim, SangYun
- Issue Date
- Feb-2024
- Publisher
- SPRINGERNATURE
- Citation
- TRANSLATIONAL PSYCHIATRY, v.14, no.1
- Journal Title
- TRANSLATIONAL PSYCHIATRY
- Volume
- 14
- Number
- 1
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/91082
- DOI
- 10.1038/s41398-024-02766-6
- ISSN
- 2158-3188
- Abstract
- Various plasma biomarkers for amyloid-beta (A beta) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma A beta 42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as A beta plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma A beta 42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET-/plasma-, PET-/plasma+, PET+/plasma-, PET+/plasma+) using Alzheimer's Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET-/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET-/plasma+ showed intermediate changes between PET-/plasma- and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma- represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma A beta 42/40 than IA-Elc. IA-Elc showed more plasma A beta 42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET-/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.
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