In the field of neurodegeneration, there is a particular need to detect biomarkers in blood that are indicative of the early onset and development of these conditions. Currently, the early stages of the major dementias are difficult to diagnose and stratify correctly, and so the treatment prescribed—even if it were the correct choice—often begins too late in the progress of the condition, leading to a poor outcome.
The term dementia covers a large class of neurodegenerative disorders with different causes and overlapping symptoms, of which Alzheimer's accounts for 62% of cases. Each disorder benefits from bespoke management and treatment by clinicians, family, and carers, but accurate diagnosis and classification are difficult and usually based on subjective observations. Degenerative syndromes can also include systemic forms; an example is amyotrophic lateral sclerosis (ALS), which results from degeneration of the upper and lower motor neurons.
Parkinson’s and Alzheimer’s, for example, have very different symptoms, but at a molecular level they may well have much in common. It is known that aggregates of specific proteins form in the brain during the progress of a neurodegenerative condition; hence, they are often referred to as protein conformation disorders. The detection of plaques, tangles, or Lewy bodies composed of specific aggregated proteins by techniques such as brain imaging in a living subject or by post-mortem histology is considered to be a confirmation of the neurological condition present. Aggregated brain-derived proteins have been detected in cerebrospinal fluid (CSF) and blood. For example, the ß-amyloid oligomer content of CSF is a promising biomarker in differentiating early Alzheimer’s from normal aging processes, as well as allowing prediction of those patients with mild cognitive impairment (MCI) who will later convert to Alzheimer’s.
Since CSF sample collection is inconvenient, often painful, and cannot easily be performed on a repeat basis, it is not a suitable procedure for routine diagnosis and screening. Aggregated biomarker proteins have also been reported to be present in blood, but at much lower concentrations, which are at the limit of measurement by the standard immunoassay instruments currently available in clinical biochemistry laboratories. The highly sensitive assay technique of surface-enhanced laser desorption time-of-flight (SELDI-TOF) mass spectrometry has been used to show that higher concentrations of ß-amyloid dimers are present in the blood of some Alzheimer’s patients, and the dimers are associated with the membranes of blood cells.
The plasma levels of various forms of α-synuclein, including oligomers, have also been shown to have potential value as a diagnostic tool in Parkinson’s syndrome.