TY - JOUR
T1 - Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET
T2 - Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease
AU - and for the AIBL Research Group
AU - Chatterjee, Pratishtha
AU - Doré, Vincent
AU - Pedrini, Steve
AU - Krishnadas, Natasha
AU - Thota, Rohith
AU - Bourgeat, Pierrick
AU - Ikonomovic, Milos D.
AU - Rainey-Smith, Stephanie R.
AU - Burnham, Samantha C.
AU - Fowler, Christopher
AU - Taddei, Kevin
AU - Mulligan, Rachel
AU - Ames, David
AU - Masters, Colin L.
AU - Fripp, Jürgen
AU - Rowe, Christopher C.
AU - Martins, Ralph N.
AU - Villemagne, Victor L.
PY - 2023/3/21
Y1 - 2023/3/21
N2 - BACKGROUND: Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD. OBJECTIVE: The objective of this study was to evaluate the association between the abovementioned astrocyte reactivity biomarkers. METHODS: Plasma GFAP and Aβ were measured using the Simoa® platform in participants who underwent brain 18F-SMBT-1 and Aβ-PET imaging, comprising 54 healthy control (13 Aβ-PET+ and 41 Aβ-PET-), 11 mild cognitively impaired (3 Aβ-PET+ and 8 Aβ-PET-) and 6 probable AD (5 Aβ-PET+ and 1 Aβ-PET-) individuals. Linear regressions were used to assess associations of interest. RESULTS: Plasma GFAP was associated with 18F-SMBT-1 signal in brain regions prone to early Aβ deposition in AD, such as the supramarginal gyrus (SG), posterior cingulate (PC), lateral temporal (LT) and lateral occipital cortex (LO). After adjusting for age, sex, APOE ɛ4 genotype, and soluble Aβ (plasma Aβ42/40 ratio), plasma GFAP was associated with 18F-SMBT-1 signal in the SG, PC, LT, LO, and superior parietal cortex (SP). On adjusting for age, sex, APOE ɛ4 genotype and insoluble Aβ (Aβ-PET), plasma GFAP was associated with 18F-SMBT-1 signal in the SG. CONCLUSION: There is an association between plasma GFAP and regional 18F-SMBT-1 PET, and this association appears to be dependent on brain Aβ load.
AB - BACKGROUND: Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD. OBJECTIVE: The objective of this study was to evaluate the association between the abovementioned astrocyte reactivity biomarkers. METHODS: Plasma GFAP and Aβ were measured using the Simoa® platform in participants who underwent brain 18F-SMBT-1 and Aβ-PET imaging, comprising 54 healthy control (13 Aβ-PET+ and 41 Aβ-PET-), 11 mild cognitively impaired (3 Aβ-PET+ and 8 Aβ-PET-) and 6 probable AD (5 Aβ-PET+ and 1 Aβ-PET-) individuals. Linear regressions were used to assess associations of interest. RESULTS: Plasma GFAP was associated with 18F-SMBT-1 signal in brain regions prone to early Aβ deposition in AD, such as the supramarginal gyrus (SG), posterior cingulate (PC), lateral temporal (LT) and lateral occipital cortex (LO). After adjusting for age, sex, APOE ɛ4 genotype, and soluble Aβ (plasma Aβ42/40 ratio), plasma GFAP was associated with 18F-SMBT-1 signal in the SG, PC, LT, LO, and superior parietal cortex (SP). On adjusting for age, sex, APOE ɛ4 genotype and insoluble Aβ (Aβ-PET), plasma GFAP was associated with 18F-SMBT-1 signal in the SG. CONCLUSION: There is an association between plasma GFAP and regional 18F-SMBT-1 PET, and this association appears to be dependent on brain Aβ load.
KW - 18F-SMBT-1
KW - Astrocyte reactivity
KW - biomarkers
KW - glial fibrillary acidic protein
KW - monoamine oxidase B
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85151045009&partnerID=8YFLogxK
U2 - 10.3233/JAD-220908
DO - 10.3233/JAD-220908
M3 - Article
C2 - 36776057
AN - SCOPUS:85151045009
SN - 1387-2877
VL - 92
SP - 615
EP - 628
JO - Journal of Alzheimer's disease : JAD
JF - Journal of Alzheimer's disease : JAD
IS - 2
ER -
