GFAP and frontotemporal dementia
Frontotemporal dementia is a heterogeneous entity with variable clinical manifestations. As a consequence, it can be confused with psychiatric diseases or other neurodegenerative diseases such as Alzheimer’s disease. Despite the advances in the diagnosis of frontotemporal dementia in the last two decades, we still do not have a precise marker for its diagnosis or to predict its evolution. Glial fibrillar acidic protein (or GFAP) is a marker of astrocytic activity, one of the main supporting cells in the central nervous system. Higher levels of this biomarker have been described in blood and cerebrospinal fluid in different neurodegenerative diseases. In the case of Alzheimer’s dementia, there are studies that link elevated levels of GFAP in blood with greater severity and functional impairment of the disease. However, little is known about the usefulness of this marker for diagnosis and for predicting the course of patients with frontotemporal dementia.
What have we done in this study?
Using novel analysis techniques, we have measured GFAP and a marker of neuronal damage (the light chain neurofilament, NfL) in plasma (blood) samples from 211 participants of the SPIN cohort at Hospital Sant Pau. Participants were patients with frontotemporal dementia, Alzheimer’s disease dementia, and cognitively healthy participants. All participants have neurological and neuropsychological evaluations where different cognitive and functional scales are assessed. In addition, most of the participants have a cerebrospinal fluid study and magnetic resonance imaging.
We measured the level of GFAP and NfL in blood samples from these participants and assessed their accuracy, individually or in combination, in differentiating frontotemporal dementia from Alzheimer’s disease and cognitively intact participants. We also determined their usefulness in predicting the evolution of frontotemporal dementia.
The main finding of this work was that levels of GFAP in blood in frontotemporal dementia differ from those in Alzheimer’s disease. This difference can be useful to differentiate the two entities. Furthermore, we have observed that higher levels of GFAP in plasma at the time of diagnosis predict greater cognitive impairment during follow-up in patients diagnosed with frontotemporal dementia. We also found an association between GFAP levels and disease severity indicators such as cortical thickness in magnetic resonance imaging and the score on cognitive and functional scales.
Relevance of the study
This study shows that the recent development of new blood markers, such as the measurement of GFAP in blood, may be useful to differentiate neurodegenerative diseases, in addition to predicting the evolution of the disease.
Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia. Zhu, N, Santos-Santos, M, Illán-Gala, I et al. Transl Neurodegener 2021