Abstract
In Alzheimer's disease, accumulation of Aβ and tau aggregates in the limbic and cortical regions of the brain forms the pathological basis for the onset of memory loss and cognitive abnormalities. The neuronal desecration inflicted by these toxic pile-ups will rouse the onset of innate immune defense mechanisms including astrogliosis within the neuronal milieu. A potential ramification of astrogliosis is the overproduction and spillage of GFAP into the brain circulation. Execution of GFAP vital physiological functions rests upon the preservation of its filamentous structure as well as its cytoskeletal interactions. Any anomaly that hampers the structural integrity of GFAP will engender filament disassembly, cytoplasmic aggregation, and decreased solubility with the resultant deleterious consequences. The potency of GFAP as a reliable biomarker in the blood also rests on its ability to navigate the glymphatic excretory pathways and spill into the systemic circulation. Recent reports have suggested GFAP is a dependable marker for auguring subtle disease changes in traumatic brain injury (TBI) and AD. However, pathological anomalies such abnormal structural integrity, cleavage, impaired drainage pathways, and alternative isoforms will lessen its potency and thwarts its ability from becoming a full-fledged and stable biomarker for neurological diseases. Understanding the GFAP biology, including factors that influence its structural integrity and excretory pathways, will be crucial and this review underscores these sections in a succinct manner. Thorough comprehension of GFAP biology is the principal step in unearthing its potential as a powerful marker for auguring disease initiation, and progression in TBI and AD.