Alzheimer’s disease detected in blood 10 years before clinical symptoms

Blood levels of glial fibrillary acidic protein (GFAP), a marker of astrogliosis, were elevated approximately 10 years before symptom onset in hereditary Alzheimer’s disease.

Three plasma biomarkers—phosphorylated tau (p-tau181), neurofilament light chain (NfL), and GFAP—were higher in mutation carriers than noncarriers in the Swedish autosomal dominant Alzheimer’s disease (ADAD) cohort. , reports Caroline Graff.Her MD, PhD, and colleagues at her Karolinska Institutet in Stockholm brain.

The trajectories show that plasma GFAP concentrations began to change ~10 years before the expected onset of AD symptoms, followed by p-tau181 ~6 years before onset and NfL ~2 years before onset. showed that.

“Overall, plasma p-tau181, GFAP, and NfL appear to be viable biomarkers for detecting a variety of Alzheimer’s-related pathologies that are already present in presymptomatic individuals,” said Graff and colleagues. writes.

“Our results suggest that plasma GFAP may reflect Alzheimer’s disease pathologies that are upstream of tangle accumulation and neurodegeneration,” they added. are limited, the implications of these findings need further examination.”

The findings are consistent with those reported in December by Dominantly Inherited Alzheimer Network researchers showing plasma GFAP elevations in hereditary Alzheimer’s disease 10 years before expected symptom onset . Other studies have shown elevated plasma GFAP in older adults at risk for Alzheimer’s disease.

“We don’t know the exact origin of the GFAP measured in plasma,” said Graff. MedPage Today“This area of ​​research is currently of great interest because it may indicate some sort of inflammatory process in the brain..”

“The value of having a marker years before expected symptoms is that it provides a very large window of opportunity for intervention or surveillance,” Graff noted. If we can stop or prevent the onset of symptoms, we may be able to delay the onset of symptoms.Measurement of GFAP may also be a marker for measuring the effectiveness of interventions.”

Emerging blood-based biomarkers for Alzheimer’s disease will help track pathology, but which disease processes can be detected in the blood or whether blood biomarkers perform well in both clinical and preclinical disease stages? It’s not clear.

Researchers evaluated 164 plasma samples from 33 ADAD mutation carriers and 42 noncarriers obtained between 1994 and 2018. ADAD is caused by mutations in the amyloid precursor protein. (app), Presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genetic; less than 1% of all cases of Alzheimer’s disease. People whose parents had Alzheimer’s disease caused by mutations have a 50% risk of developing the disease.

Study participants came from two app family (APPswe When APParc) and one PSEN1 family. ADAD can use the family mean age of onset to estimate the expected age of onset for at-risk individuals. The mean age at onset was her 54 years. APPswe 56 mutation carriers APParcand 52 PSEN1 family.

Carrier and non-carrier characteristics showed no statistical difference in baseline age, expected year of onset, or proportion of patients. APOE4 allele, and gender. A mixed-effects model showed that plasma concentrations of NfL, GFAP, and p-tau181, but not total tau, were increased in carriers compared with non-carriers. Plasma p-tau181 correlated with levels of total tau and p-tau181 in cerebrospinal fluid.

“We would like to replicate this study using a larger sample set,” said Graff. “We plan to increase the number of samples of the same individual and increase the number of individuals from families with ADAD.”

The findings also “strongly suggest that sporadic Alzheimer’s disease research should be done because the underlying pathology of hereditary and sporadic Alzheimer’s disease is the same,” she said. rice field.