Astrogliosis instigated signature in neurodegenerative diseases: Supremacy of GFAP in forecasting structural pathology and disease progression in Alzheimer’s disease

Abstract

In Alzheimer Disease, accumulation of Aβ and tau aggregates in the vicinity of neuro-synaptic junction is bound to stir up a potpourri of compensatory glial modifications that tend to backpedal the neurotoxic damage and revitalize the physiological equilibrium. In this regard, astrogliosis is a protective mechanism that serves to counterbalance these neuronal mutilations during various stages of pathogenesis in AD. A spin-off of astrogliosis is exuberant production of markers such as GFAP. GFAP is a 50kDa cytoskeletal protein comprising of head domain, rod domain and tail domain. The sovereign function of GFAP is to promote neuronal growth, synaptic plasticity, and myelination. Its cardinal isoform is GFAP- α but it can exist in different isoforms based on alternative splicing of parent mRNA. Throughout physiological conditions, GFAP absconds from the brain by fleeing through para-vascular route and glymphatic pathways to enter the systemic circulation. Unfortunately, CSF GFAP does not live up to the expectations as reliable marker for broadcasting subtle cellular and structural changes in AD. On the contrary, serum GFAP championed itself as an acclaimed marker that can consistently omen accumulation of structural changes, stockpiling of Aβ42/40 and tau aggregates in PET scan, cognitive impairment, and dementia in pre-clinical and clinical AD patients. This review contributes to bridge the current knowledge gap in physiology, excretory pathways, and clinical significance of plasma GFAP as a glorious biomarker in AD. Hopefully, we propound further research studies for cementing its position as a high-powered marker for auguring disease initiation, evolution, progression in AD.

Keywords

• neuronal death
• brain atrophy
• amyloid beta
• tau
• neurodegeneration
• biomarkers