Blood-Based Markers May Reveal Alzheimer’s Disease Ten Years Before Symptoms Show

Summary: A new blood test can detect the GFAP protein at elevated levels in blood samples up to ten years before symptoms of Alzheimer’s disease are first noticeable in those with an inherited form of the neurodegenerative disorder.

Source: Karolinska Institute

Alzheimer’s disease begins decades before the onset of any symptoms, such as memory loss. Consequently, early diagnosis increases the chances of slowing the disease down with drugs.

A new study on an inherited form of the disease shows that a protein called GFAP is a possible biomarker for very early stages of the disease.

The study, conducted by researchers at Karolinska Institutet and published in the journal Brain, could one day lead to an earlier detection of this serious and common disease.

“Our results suggest that GFAP, a presumed biomarker for activated immune cells in the brain, reflects changes in the brain due to Alzheimer’s disease that occur before the accumulation of tau protein and measurable neuronal damage,” says the study’s first author Charlotte Johansson, doctoral student at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Sweden.

“In the future it could be used as a non-invasive biomarker for the early activation of immune cells such as astrocytes in the central nervous system, which can be valuable to the development of new drugs and to the diagnostics of cognitive diseases.”

Alzheimer’s disease causes 60 to 70% of all dementia cases, according to the Swedish Brain Foundation. In Alzheimer’s disease, nerve cells in the brain degenerate as a result of the abnormal accumulation of the proteins beta-amyloid and tau. As more brain neurons become damaged, this manifests in dysfunction of cognitive functions such as memory and speech.

The disease progresses insidiously and biological changes in the brain begin already 20 to 25 years before memory loss and other cognitive symptoms become evident. The earlier a patient is correctly diagnosed, the sooner he or she can be offered the right treatment. This is one of many reasons why more research is needed on precise, easy-to-use methods of early diagnosis.

This shows blood samples
A new study on an inherited form of the disease shows that a protein called GFAP is a possible biomarker for very early stages of the disease. Image is in the public domain

Researchers at Karolinska Institutet and their colleagues at Landspitali University Hospital in Iceland, Gothenburg University and University College London in the UK have been studying biomarkers in blood for very early pathological changes in a rare and inherited form of Alzheimer’s disease that accounts for less than 1% of all cases. Individuals with a parent with Alzheimer’s disease caused by a mutation have a 50% risk of developing the disease themselves.

For their study, the researchers analyzed 164 blood plasma samples from 33 mutation carriers and 42 relatives without the inherited pathogenic predisposition. The data were collected between 1994 and 2018.

Their results reveal clear changes of several blood protein concentrations in the mutation-carriers.

“The first change we observed was an increase in GFAP (glial fibrillary acidic protein) approximately ten years before the first disease symptoms,” says the study’s last author Caroline Graff, professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

“This was followed by increased concentrations of P-tau181 and, later, NfL (neurofilament light protein), which we already know is directly associated with the extent of neuronal damage in the Alzheimer’s brain. This finding about GFAP improves the chances of early diagnosis.”

About this Alzheimer’s disease research news

Author: Press Office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: The image is in the public domain

Original Research: Open access.
Plasma biomarker profiles in autosomal dominant Alzheimer disease” by Charlotte Johansson et al. Brain


Plasma biomarker profiles in autosomal dominant Alzheimer disease

Emerging plasma biomarkers of Alzheimer’s disease might be non-invasive tools to trace early Alzheimer’s disease-related abnormalities such as the accumulation of amyloid-beta peptides, neurofibrillary tau tangles, glial activation and neurodegeneration. It is, however, unclear which pathological processes in the CNS can be adequately detected by peripheral measurements and whether plasma biomarkers are equally applicable in both clinical and preclinical phases. Here we aimed to explore the timing and performance of plasma biomarkers in mutation carriers compared to non-carriers in autosomal dominant Alzheimer’s disease.

Samples (n = 164) from mutation carriers (n = 33) and non-carriers (n = 42) in a Swedish cohort of autosomal dominant Alzheimer’s disease (APP p.KM670/671NL, APP p.E693G and PSEN1 p.H163Y) were included in explorative longitudinal analyses. Plasma phosphorylated tau (P-tau181), total tau (T-tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) concentrations were measured with a single-molecule array method as previously described. Plasma biomarkers were additionally correlated to Alzheimer’s disease core biomarkers in the CSF.

Results from the longitudinal analyses confirmed that plasma P-tau181, NfL and GFAP concentrations were higher in mutation carriers compared to non-carriers. This change was observed in the presymptomatic phase and detectable first as an increase in GFAP approximately 10 years before estimated symptom onset, followed by increased levels of P-tau181 and NfL closer to expected onset. Plasma P-tau181 levels were correlated to levels of P-tau181 and T-tau in the CSF.

Altogether, plasma P-tau181, GFAP and NfL seem to be feasible biomarkers to detect different Alzheimer’s disease-related pathologies already in presymptomatic individuals. Interestingly, changes in plasma GFAP concentrations were detected prior to P-tau181 and NfL. Our results suggest that plasma GFAP might reflect Alzheimer’s disease pathology upstream to accumulation of tangles and neurodegeneration. The implications of these findings need additional validation, in particular because of the limited sample size.

Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.
We hate spam and only use your email to contact you about newsletters. You can cancel your subscription any time.