Biomarkers in the diagnosis and management of Alzheimer's disease

Traditionally Alzheimer's disease (AD) has been diagnosed and its course followed based on clinical observations and cognitive testing, and confirmed postmortem by demonstrating amyloid plaques and neurofibrillary tangles in the brain. But the growing recognition that the disease process is ongoing, damaging the brain long before clinical findings appear, has intensified a search for biomarkers that might allow its very early diagnosis and the objective assessment of its responses to putative treatments. At present at least eight biochemical measurements or scanning procedures are used as biomarkers, usually in panels, by neurologists and others. The biochemical measurements are principally of amyloid proteins and their A-beta precursors, or of tau proteins. Brain atrophy can be assessed by means of structural magnetic resonance imaging (sMRI), and decreased blood flow and metabolism can be estimated by functional magnetic resonance imaging (fMRI). [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is used to measure the brain's energy utilization and to infer synaptic number. Impaired connectivity between brain regions is indicated by diffusion tensor imaging (DTI), while magnetic resonance spectroscopy (MRS) provides metabolic markers of diminished cell number. Additional proposed biomarkers utilize electroencephalography (EEG) and magnetoencephalography (MEG) for quantifying impairments in connectivity. Genetic analyses illustrate the heterogeneity of disease processes that can cause cognitive impairment syndromes. Recent observations awaiting confirmation suggest that levels of some plasma phospholipids can also be biomarkers of AD and that reductions in these levels can enable the accurate prediction that a cognitively normal individual will go on to develop MCI or AD within 2 years.