Abstract
Background
The astrocyte cytoskeletal protein, Glial Fibrillary Acidic Protein (GFAP), is a potential blood-based biomarker for diagnosis and prognosis of older adults in the Alzheimer’s Disease (AD) continuum, comprising cognitively unimpaired (CU) and cognitively impaired individuals with high brain amyloid-beta load (Aβ+). However, specific attention to the potential of plasma GFAP in CU Aβ+ older adults with Subjective Memory Complaints (SMCs) is required, given that SMCs are a primary feature of Subjective Cognitive Decline (SCD) and individuals with SMCs are twice as likely to develop dementia compared to non-memory complainers.
Method
Plasma GFAP was measured in older adults with SMCs from two independent cohorts, namely the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH; N = 76; 52 Aβ-, 24 Aβ+) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL; N = 75; 50 Aβ-, 25 Aβ+), using the Neurology-4PlexA and Neurology-4PlexE kits, respectively, on the Single Molecule Array (Simoa) platform (Quanterix). The Memory Assessment Clinic-Q was used to assess participants with SMCs.
Result
Plasma GFAP was significantly elevated in Aβ+ SMCs compared with Aβ- SMCs in both cohorts before and after adjusting for age, sex and APOE ε4 carrier-status (mean±SD in pg/mL; KARVIAH: Aβ- = 148±47, Aβ+ = 230±93, p<.0001; AIBL: Aβ- = 135±58, Aβ+ = 209±76, p<.0001). Plasma GFAP differentiated Aβ+ SMCs from Aβ- SMCs with an area under the receiver operating characteristic curve (AUC) of 80% (CI:68%-92%) in KARVIAH and 77% (CI:66%-89%) in AIBL. Based on the AUC, plasma GFAP performed equivalent to other putative plasma AD diagnostic markers such as plasma phosphorylated-tau181 (p-tau181) and plasma Aβ42/Aβ40 ratio but performed significantly better than plasma Neurofilament Light (NfL) in both cohorts (p<.05). A model comprising plasma GFAP, p-tau181, Aβ42/Aβ40 ratio and the AD risk factors, age, sex and APOE ε4 carrier-status significantly outperformed any of the biomarkers alone in differentiating brain Aβ-/+ status in both cohorts (p<.05). Higher plasma GFAP in individuals with SMCs was associated with faster cognitive decline assessed by the Preclinical Alzheimer Cognitive Composite (PACC) score and with faster brain Aβ accumulation assessed by PET in AIBL.
Conclusion
These observations suggest that plasma GFAP has diagnostic and prognostic value for older adults at risk for AD.