Glial fibrillary acidic protein

Glial fibrillary acidic protein (GFAP) is a class-III intermediate filament that serves as a cell-specific marker for astrocytes in the central nervous system (UniProt: P14136). It plays a key role in distinguishing astrocytes from other glial cells during CNS development and helps maintain the structural integrity of astrocytic cytoplasm.

GFAP is primarily expressed in astrocytes throughout the brain and spinal cord. Mutations in GFAP cause Alexander disease (MIM 203450), a rare leukodystrophy characterized by progressive white matter degeneration, macrocephaly, seizures, and the pathological hallmark of Rosenthal fiber accumulation in astrocytes (UniProt: P14136).

In Alzheimer's disease, GFAP is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 2.61 (Chaparral AD proteomics). This elevation is consistent with reactive astrogliosis observed in AD pathology, where astrocytes become activated in response to amyloid-β accumulation and neuroinflammatory signaling, contributing to the neuroinflammatory landscape of the disease.