The National Institute of Aging has initiated the Alzheimer’s Disease Neuroimaging Initiative, a large observational study of patients with Alzheimer’s Disease (AD), patients with mild cognitive impairment and cognitively normal volunteers to assess longitudinal changes in AD. Because cognitive measures do not easily correlate disease-modifying effects of treatment, current trials of investigational compounds require large sample sizes and long treatment duration. Therefore the use of biomarkers in such trials can help in the understanding of disease progression and drug effect.
Biomarkers allow new therapies to be developed more quickly and can be directly associated with a drug treatment as companion diagnostic. Since a clinical diagnosis of Alzheimer disease is inaccurate even among experienced investigators in about 10% to 15% of cases, biomarkers might improve the accuracy of diagnosis. Indeed it is mandatory in a diagnosis to exclude other forms of dementia as fronto-temporal lobe degeneration (FTLD), dementia with Lewy bodies (DLB) and vascular dementia (VaD). In addition biomarkers might also serve as indirect measures of AD severity and could help to follow the evolution of the disease during a drug treatment. There are two directions in developing biomarkers of AD: (i) neuroimaging techniques which provide both structural and metabolic information about the brain, (ii) and cerebrospinal fluid (CSF) biomarkers which correlate the intensity of the disease. Cerebrospinal fluid (CSF) collection is a test to look at the fluid that surrounds the brain and spinal cord, and is performed through a ‘lumbar puncture’. The CSF acts as a cushion, protecting the brain and spine from injury. The fluid is normally clear.
A biomarker is “A specific physical trait used to measure or indicate the effects or progress of a disease or condition“. The role of a biomarker is to provide doctors with an accurate and a reliable tool to make a diagnosis of Alzheimer’s disease. With degenerative diseases such as Alzheimer’s a biomarker should ideally, many doctors believe, meet a number of criteria.
According to a recent review, the identification and validation of biomarkers for diagnosing Alzheimer’s disease and other forms of dementia are increasingly important. To date, biochemical measurements of ?-amyloid(1-42), total tau and phospho-tau-181 in cerebrospinal fluid (CSF) is the most advanced and accepted method to diagnose probable AD with high specificity and sensitivity. Specificity means that a test can pick up an abormality in that particular condition, rather than other conditions; sensitivity means that it’s very adept at doing so. Biomarkers should be totally reliable, obtaining the sample should be simple, should have few side effects, and should be cheap.
However, it is a great challenge to search for novel biomarkers in CSF and blood by using modern mega-sophisticated biochemical methods, such as microarrays and mass spectrometry, and to optimize the handling of samples (e.g. collection, transport, processing, and storage), as well as the interpretation using biological metrics.
It seems likely that only a combined analysis of several biomarkers will define a patient-specific signature to diagnose AD in the future.
