Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Complex interplay of astrogliosis and pathology in preclinical Alzheimer's disease.
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Gogola Alexandra, Minhas Davneet, Lopresti Brian, Snitz Beth, Reese Alexandria C, Matan Cristy, Wu Minjie, Zeng Xuemei, Saeed Anum, Reis Steven, Aizenstein Howard, Ikonomovic Milos D, Lopez Oscar, Karikari Thomas, Cohen Ann, Villemagne Victor L
Аннотация
INTRODUCTION: We evaluated the effects of astrogliosis on Alzheimer's disease (AD) pathology, co-pathology, and symptoms.
METHODS: Cross-sectional data from 187 non-demented participants were processed to obtain measures of SMBT-1 standard uptake value ration (SUVR), plasma glial fibrillary acidic protein (GFAP), β-amyloid (Aβ), Centiloids (CL), tau (CenTauR), white matter hyperintensities (WMH), hippocampal volume (HV), and cognition. Linear regressions evaluated pairwise associations, linear regression interaction terms indicated moderating association, and causal mediation analysis evaluated mediating associations.
RESULTS: Astrogliosis was associated with CL (p < 0.01), neurodegeneration (0.05 < p < 0.1), and global cognition (p < 0.01). Moderation analyses revealed SMBT-1 SUVR had an attenuating interaction with CL in respect to CenTauR (β = -0.13, p = 0.0006) and memory impairment (β = 0.064, p = 0.05). Plasma GFAP had an attenuating interaction with CL in respect to CenTauR (β = -0.19, p = 0.00001).
DISCUSSION: Reactive astrogliosis is an early and important player in the AD development pathway by having an early attenuating effect against Aβ. More work is needed to further understand these complex associations.
METHODS: Cross-sectional data from 187 non-demented participants were processed to obtain measures of SMBT-1 standard uptake value ration (SUVR), plasma glial fibrillary acidic protein (GFAP), β-amyloid (Aβ), Centiloids (CL), tau (CenTauR), white matter hyperintensities (WMH), hippocampal volume (HV), and cognition. Linear regressions evaluated pairwise associations, linear regression interaction terms indicated moderating association, and causal mediation analysis evaluated mediating associations.
RESULTS: Astrogliosis was associated with CL (p < 0.01), neurodegeneration (0.05 < p < 0.1), and global cognition (p < 0.01). Moderation analyses revealed SMBT-1 SUVR had an attenuating interaction with CL in respect to CenTauR (β = -0.13, p = 0.0006) and memory impairment (β = 0.064, p = 0.05). Plasma GFAP had an attenuating interaction with CL in respect to CenTauR (β = -0.19, p = 0.00001).
DISCUSSION: Reactive astrogliosis is an early and important player in the AD development pathway by having an early attenuating effect against Aβ. More work is needed to further understand these complex associations.