Gfap, the glial fibrillary acidic protein, is an astrocytic cytoskeletal protein. It plays a crucial role in maintaining the structure and function of astrocytes in the central nervous system. Its function is associated with astroglial activation and astrocytosis, which are important processes in various neurological conditions [1,3,4].

Multiple studies have explored Gfap's significance in different diseases. In Alzheimer's disease, blood Gfap levels are higher in the Aβ-positive group, as well as in individuals with AD or mild cognitive impairment compared to healthy controls, suggesting its potential as a biomarker for early-stage AD [1]. Plasma Gfap is an early marker associated with brain amyloid-β pathology but not tau aggregation, even in cognitively normal individuals with a normal amyloid-β status, and it mediates the early association between soluble and insoluble Aβ [3,4]. In autoimmune Gfap astrocytopathy, over half of the patients presented with movement disorders, autonomic dysfunction, and hyponatremia [2]. Peripheral Gfap levels increase up to 15 years before dementia diagnosis, and elevation of Gfap increases the risk for several types of dementia, indicating its potential as a biomarker for early-stage dementia [5]. In neurodegenerative dementias, plasma Gfap allows discrimination of disease groups from healthy controls and differentiates AD from frontotemporal dementia, though with lower accuracy than other biomarkers [6]. Additionally, Gfap has diagnostic and prognostic value in traumatic brain injury and intracranial hemorrhage, with higher plasma concentrations associated with these conditions [7,9]. Alexander disease is caused by dominantly acting mutations in Gfap, leading to a gain-of-function sometimes referred to as "Gfap toxicity" [8].

In conclusion, Gfap is essential for the normal function of astrocytes and is involved in various neurological diseases. Its role as a biomarker in diseases like Alzheimer's, dementia, and in the diagnosis and prognosis of traumatic brain injury and intracranial hemorrhage is significant. The understanding of Gfap's function in these disease conditions, though not specifically from KO/CKO mouse models in the provided references, helps in developing diagnostic and therapeutic strategies for related neurological disorders.

References:

1. Kim, Ka Young, Shin, Ki Young, Chang, Keun-A. 2023. GFAP as a Potential Biomarker for Alzheimer's Disease: A Systematic Review and Meta-Analysis. In Cells, 12, . doi:10.3390/cells12091309. https://pubmed.ncbi.nlm.nih.gov/37174709/

2. Kimura, Akio, Takekoshi, Akira, Yoshikura, Nobuaki, Hayashi, Yuichi, Shimohata, Takayoshi. 2019. Clinical characteristics of autoimmune GFAP astrocytopathy. In Journal of neuroimmunology, 332, 91-98. doi:10.1016/j.jneuroim.2019.04.004. https://pubmed.ncbi.nlm.nih.gov/30991306/

3. Pereira, Joana B, Janelidze, Shorena, Smith, Ruben, Blennow, Kaj, Hansson, Oskar. . Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer's disease. In Brain : a journal of neurology, 144, 3505-3516. doi:10.1093/brain/awab223. https://pubmed.ncbi.nlm.nih.gov/34259835/

4. Pelkmans, Wiesje, Shekari, Mahnaz, Brugulat-Serrat, Anna, Suarez-Calvet, Marc, Gispert, Juan Domingo. 2023. Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression. In Alzheimer's & dementia : the journal of the Alzheimer's Association, 20, 483-493. doi:10.1002/alz.13450. https://pubmed.ncbi.nlm.nih.gov/37690071/

5. Wang, Xiaofei, Shi, Ziyan, Qiu, Yuhan, Sun, Dongren, Zhou, Hongyu. 2024. Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank. In BMC medicine, 22, 192. doi:10.1186/s12916-024-03418-8. https://pubmed.ncbi.nlm.nih.gov/38735950/

6. Baiardi, Simone, Quadalti, Corinne, Mammana, Angela, Capellari, Sabina, Parchi, Piero. 2022. Diagnostic value of plasma p-tau181, NfL, and GFAP in a clinical setting cohort of prevalent neurodegenerative dementias. In Alzheimer's research & therapy, 14, 153. doi:10.1186/s13195-022-01093-6. https://pubmed.ncbi.nlm.nih.gov/36221099/

7. Korley, Frederick K, Jain, Sonia, Sun, Xiaoying, Diaz-Arrastia, Ramon, Manley, Geoffrey T. . Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study. In The Lancet. Neurology, 21, 803-813. doi:10.1016/S1474-4422(22)00256-3. https://pubmed.ncbi.nlm.nih.gov/35963263/

8. Messing, Albee. 2019. Refining the concept of GFAP toxicity in Alexander disease. In Journal of neurodevelopmental disorders, 11, 27. doi:10.1186/s11689-019-9290-0. https://pubmed.ncbi.nlm.nih.gov/31838996/

9. Zylyftari, Sabina, Luger, Sebastian, Blums, Kristaps, Kalra, Love-Preet, Foerch, Christian. 2024. GFAP point-of-care measurement for prehospital diagnosis of intracranial hemorrhage in acute coma. In Critical care (London, England), 28, 109. doi:10.1186/s13054-024-04892-5. https://pubmed.ncbi.nlm.nih.gov/38581002/