Cerebrospinal Fluid Based Diagnosis in Alzheimer’s Disease

The Alzheimer’s disease (AD) is the most frequent form of dementia worldwide. The major neuropathological hallmarks of the disease are loss of neurons and synapse, senile plaques (extracellular aggregates primarily composed of ß-amyloid; Aß) and neurofibrillary tangles (aggregates of hyperphosphorylated forms of the microtubule-associated tau protein) throughout cortical and limbic regions of the brain. The definite diagnosis still requires histopathological conformation according to the criteria, however, in recent years substantial progress has been made in the area of early biomarker development. The use of cerebrospinal fluid as a testing platform is very promising because the CSF protein composition can reflect the pathological processes of the brain and because it is easily accessible by a lumbar puncture. Some proteins and peptides such as ß-amyloid 1-42 (A┚142), ß-amyloid 1-40 (A┚1-40), total tau (tau) and hyperphosphorylated tau (p-tau) have been reported to meet the criteria for a biomarker. Another series of publications reported transthyretin, isoprostane, BACE1 activity and other proteins and enzymes as a potential biomarkers in AD. Whereas the biomarkers mentioned first have been studied extensively and were suggested to be included into clinical AD criteria, less information is available on the others. This review will focus on the importance of CSF based biomarkers in AD, covers the data available from the literature and highlights their role in the differential diagnosis of dementia.