The Role of Proteins in Early Diagnosis

The key to identifying Alzheimer’s disease at an early stage may lie in proteins. Neurodegenerative disorders like Alzheimer’s and Parkinson’s are characterized by issues related to protein aggregation. Misfolded proteins can form insoluble clumps that disrupt normal cellular function, exemplified by the plaques and tangles associated with Alzheimer’s.

Crucially, these protein-related issues can begin to arise years before any symptoms are evident. For instance, changes in the levels and ratios of amyloid beta proteins (Aβ42 and Aβ40) in cerebrospinal fluid can be detected up to nine years prior to the onset of dementia. Similarly, the presence of α-synuclein aggregates can be found in individuals destined to develop Parkinson’s disease long before any clinical signs appear.

However, current testing methods often rely on cerebrospinal fluid, which is not a routine part of standard medical checkups. Without participation in clinical trials, individuals typically undergo these tests only after experiencing symptoms—making timely diagnosis increasingly difficult.

Introducing the GFET Biosensor

To address this challenge, researchers have developed a prototype biosensor utilizing graphene field-effect transistor (GFET) technology. Originally designed to detect SARS-CoV-2, this platform has been adapted to identify specific protein biomarkers for Alzheimer’s and Parkinson’s diseases.

The biosensor employs aptamers—short strands of DNA or RNA that bind to specific target molecules. When these aptamers attach to biomarkers such as amyloid beta and tau proteins, they induce a change in the electric charge on the graphene surface of the sensor.

To evaluate the sensor's sensitivity and accuracy, researchers tested it against various concentrations of synthetic disease-related proteins. Results demonstrated that the biosensor could detect extremely low concentrations, even in the femtomolar range, and successfully differentiated between the target proteins linked to neurodegenerative diseases.

Additionally, the GFET biosensor was tested on brain samples from deceased individuals with Alzheimer’s or Parkinson’s disease, yielding promising results in identifying these proteins, even in diluted samples.

While the findings are promising, researchers recognize certain limitations. Detecting amyloid proteins from brain tissue in bodily fluids necessitates meticulous sample preparation to prevent contamination. Furthermore, regional, genetic, and population differences may require the development of more specific aptamers to account for minor variations in the amino acid sequences of the target molecules.

Nevertheless, if researchers can refine this sensor for use with blood or saliva from living individuals, it could represent a significant advancement in early diagnosis.