Biological markers of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease that affects cognition, behavior, and function. The etiology of the disease is unknown; however, the primary risk factors for AD are aging and family history. Neurofibrillary tangles (NFT) and amyloid-bearing neuritic plaques in the limbic and cerebral cortices are the characteristic neuropathologic lesions in brains of patients with AD. The NFT is mainly composed of hyperphosphorylated tau, whereas the major component of the neuritic plaques is the amyloid beta (A(3) protein. The clinical diagnosis of probable AD is based on history, physical examination, neuropsychological testing, laboratory studies, and neuroimaging techniques. However, there is no laboratory marker to support the diagnosis of definite AD or monitoring the progression of the disease. Several biochemical markers related to neuropathology have been identified in cerebrospinal fluid (CSF). We describe the studies of CSF or blood levels of tau protein, amyloid (3 protein, amyloid precursor protein isoforms, neuronal thread protein, and iron-binding protein (p97) in patients with AD and age-matched nondemented controls. Due to the heterogeneity and complex nature of the disease, it is highly unlikely that a single marker specific for AD will be found. However, a panel of biomarkers may help to discriminate different subgroups of AD with distinct genetic backgrounds. (C) 2002 Wiley-Liss, Inc.