Alzheimer’s disease detectable by blood biomarkers 10 years before clinical symptoms

Hereditary Alzheimer’s disease (AD) can be diagnosed very early on by levels of a protein called ‘glial fibrillary acidic protein’ (GFAP) in an individual’s plasma, according to a journal article. Research claims. brain (“Plasma biomarker profile in autosomal dominant Alzheimer’s disease”). This study also corroborates previous findings on changes in plasma phosphorylated tau 181 (P-tau 181) and neurofilament light chain (NfL) levels, whereas changes in plasma GFAP concentrations were associated with his P -The study found that it precedes changes in Tau181 and NfL.

Early diagnosis of any disease offers the opportunity for earlier treatment and better outcomes. This is especially true in progressive neurodegenerative diseases such as AD, where pathological processes begin to take root in the brain decades before clinical symptoms of dementia become evident.

Researchers at the Karolinska Institutet in Sweden, along with collaborators at Landspitari University Hospital in Iceland, the University of Gothenburg, and University College London, UK, by comparing 33 individuals with autosomal dominant mutations. , conducted a longitudinal study to investigate the diagnostic power of plasma biomarkers. 42 individuals without such mutations known to cause Alzheimer’s disease.

“Our results show that GFAP, a putative biomarker of activated immune cells in the brain, reflects Alzheimer’s disease-induced brain changes that precede tau protein accumulation and measurable neuronal damage. suggests that,” says a doctoral student in the Department of Neurobiology, Care Sciences and Sociology at the Karolinska Institutet. “In the future, it could be used as a non-invasive biomarker for early activation of immune cells such as astrocytes in the central nervous system, which could aid in the development of new drugs and the diagnosis of cognitive diseases.”

Autopsy studies over the years have established that progressive neurodegeneration and inflammatory glial activation in Alzheimer’s disease are associated with the accumulation of beta-amyloid plaques and tau tangles in the brain parenchyma. These abnormalities eventually manifest as cognitive deficits in memory and speech.

Despite the increase in AD, which affects nearly 70% of people with dementia in recent years, detecting the disease in its early stages remains a challenge. It is unclear whether changes detected in the peripheral circulation during early (presymptomatic) and late (clinical) stages truly reflect the pathological progression of the disease in the brain. These unanswered questions have prompted investigations into the timing and performance of plasma biomarkers in AD.

Individuals with AD whose parent is caused by a genetic lesion have a 50% chance of developing the disease. These rare genotypes of AD make up her less than 1% of all AD patients.

In the current study on 164 plasma samples collected between 1994 and 2018, results show changes in some blood protein levels in mutation carriers. The samples included 33 individuals from individuals with mutations in the genes amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2), known to cause autosomal dominant Alzheimer’s disease (ADAD). A plasma sample was included.

“The first change we observed was an increase in GFAP about 10 years before the first disease symptoms,” said senior author of the study, professor of neurobiology, care sciences and society. Dr. Caroline Graff said. “This was followed by an increase in the concentration of P-tau181, followed by an increase in the concentration of NfL (neurofilament photoprotein), which has already been directly associated with the degree of neuronal damage in the Alzheimer’s brain. We know, this discovery of GFAP raises the possibility of early diagnosis.”

Potentially diagnostic peripheral perturbations of GFAP need to be validated in further studies to translate these findings into a clinical diagnostic tool.

This research was sponsored by grants from the Swedish Brain Foundation, Swedish Alzheimer’s Foundation, and the ALF Project.