Towards PET Scan Detection of α-Synuclein for Early Diagnosis of Parkinson’s Disease

Researchers here note recent progress towards assessment of the burden of misfolded α-synuclein in a living brain via contrast imaging. This would provide a way to reliably diagnose Parkinson’s disease in advance of symptoms. Unlike imaging for the protein aggregates associated with Alzheimer’s disease, this is not an established capability. It seems likely that imaging approaches will fade in importance in the years ahead, however, as blood assays with a much lower cost are now demonstrated to be able to detect neurodegenerative diseases in their earliest stages.

The abnormal accumulation of α-synuclein protein is a defining pathological feature of several neurodegenerative conditions collectively known as synucleinopathies, including Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Until recently, confirming the presence of these protein aggregates required post-mortem examination, severely limiting early diagnosis and treatment monitoring capabilities.

A recent paper meticulously reviews recent advances in positron emission tomography (PET) tracer development, with special attention to promising candidates that have shown effectiveness in both laboratory and clinical settings. The researchers highlight tracers such as [18F]F-0502B, [18F]C05-05, and [18F]ACI-12589, which have demonstrated encouraging results in distinguishing patients with synucleinopathies from healthy controls.

One particularly significant breakthrough came when [18F]C05-05 successfully visualized synucleinopathies in ten patients meeting clinical diagnostic criteria for Parkinson’s disease or dementia with Lewy bodies. This tracer showed increased binding in the midbrain – an area commonly affected by Lewy body pathologies – and this binding correlated well with the severity of motor symptoms.

Despite these developments, several challenges that remain in developing optimal α-synuclein PET tracers. The heterogeneous distribution and conformation of α-synuclein aggregates across different synucleinopathies, along with the relatively low density of these pathological features, complicate the development of universally effective imaging agents.