High risk of obstructive sleep apnoea is associated with higher baseline plasma glial fibrillary acidic protein and predicts decline in levels over time in cognitively unimpaired older adults.

Background: Findings from animal studies report links between obstructive sleep apnoea (OSA) models and elevated glial fibrillary acidic protein (GFAP). In humans, elevated plasma GFAP, reflecting reactive astrogliosis, is considered an early event in the Alzheimer's disease (AD) continuum. The current study investigated whether OSA risk predicts the slope of plasma GFAP in cognitively unimpaired older adults. Method: Linear mixed effect model analyses were conducted on 70 cognitively unimpaired older adult (M = 73.1, SD = 5.2, 57.1% female) participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. Individuals completed the well‐validated STOP‐Bang questionnaire to assess OSA risk (Low; Intermediate; High), and underwent positron emission tomography (PET) to quantify brain Aβ burden. Plasma GFAP was measured using the Simoa® platform over three timepoints (range 30.06 ‐ 99.45 months). The model included, a random intercept, a three‐way interaction between OSA risk, baseline brain Aβ status and time, adjusting for Apolipoprotein E (APOE) ε4 status, sex, baseline age, and baseline body mass index. Result: High risk of OSA and high brain Aβ (>25 Centiloids) were independently associated with higher baseline plasma GFAP and forecast a negative longitudinal plasma GFAP trajectory. Conclusion: These novel findings suggest that OSA mechanisms, independent of prior brain Aβ accumulation, may contribute to early reactive astrogliosis in cognitively unimpaired older adults. Additionally, a decline in plasma GFAP was observed during the preclinical period, both in those at high risk of OSA and those at greater risk of AD due to high brain Aβ. [ABSTRACT FROM AUTHOR]