GFAP in plasma and CSF in Down syndrome and Alzheimer’s disease

Alzheimer’s Disease, Down Syndrome and GFAP

People with Down syndrome are at higher risk of developing Alzheimer’s disease than the general population. In fact, by the age of 70, more than 95% of people with Down syndrome will develop Alzheimer’s disease, which is the leading cause of death in this population. This strong association is due to the triplication of a gene that is involved in the development of Alzheimer’s disease called amyloid precursor protein and located on chromosome 21. In people with Down syndrome, early detection of Alzheimer’s disease is a clinical challenge. The change in cognitive functioning can be difficult to determine due to the different levels of intellectual disability associated with the syndrome. Biomarkers such as the GFAP protein could be useful to assess diagnosis and prognosis.

The eBioMedicine journal recently published our study entitled: “Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study”. This study is the result of collaboration between the Memory Unit – Alzheimer-Down Unit of the Hospital de Sant Pau, the University of Gothenburg, the Ludwig-Maximilians-Universität of Munich, and the Alzheimer’s and other cognitive disorders Unit of the Hospital Clínic.

GFAP - Sant Pau Memory Unit

What have we done in this study?

In this study, we investigated the potential of glial fibrillary acidic protein (GFAP), in blood (plasma) and cerebrospinal fluid as a diagnostic and prognostic biomarker for Alzheimer’s disease in people with Down syndrome. We compared their changes with those of autosomal dominant and sporadic Alzheimer’s disease.

We analyzed samples from 997 participants from the DABNI and SPIN together with samples of participants from the H. Clínic and the Ludwig-Maximilians-Universität. We included samples of participants with Down syndrome, autosomal dominant Alzheimer’s, sporadic Alzheimer’s disease, and volunteers without cognitive problems. GFAP concentrations in the participants’ cerebrospinal fluid and blood were measured, and imaging tests were performed to assess for the presence of amyloid pathology and changes in brain structure.

Main results on GFAP

The results show that plasma GFAP concentration is the biomarker that changes the most throughout the progression of Alzheimer’s disease, increasing from the early preclinical stages to the dementia phase. In addition, we compared the dynamics of Alzheimer’s disease in Down syndrome and autosomal dominant Alzheimer’s disease, and found that the two types of disease exhibit changes in GFAP that begin in parallel with decreased CSF Aβ levels over 25 years before symptom onset and 10 years before increases in Aβ uptake on PET.

Plasma GFAP was also useful in discriminating between people with symptomatic and asymptomatic Alzheimer’s disease and was able to predict disease progression and cognitive decline in the dementia stage. Furthermore, plasma GFAP levels were associated with brain Aβ pathology as measured by PET.

Implications of the study

The results of this study support the utility of GFAP as a biomarker of Alzheimer’s disease in adults with Down syndrome. This has important implications for clinical practice and clinical trial design, as the GFAP could be used to identify those who are most at risk of developing the disease and to assess the efficacy of treatments under development.

More information

The study received funding from Fundació La Caixa, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jérôme Lejeune Foundation, AC Immune, Medical Research Council, Alzheimer’s Association, National Institute for Health Research, EU Joint Programme–Neurodegenerative Disease Research, Alzheimer’s society and Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens und Umwelteinflüssen auf die menschliche Gesundheit.

We thank all study participants, their families, and their caregivers for their support and dedication to this research.

Details of the study can be found at this link:

Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study. Montoliu-Gaya, L, Alcolea, D, Ashton, NJ et al. EBioMedicine 2023

Leave a Comment