The role of biological markers in the early and differential diagnosis of Alzheimer's disease.

Biological markers can be used to identify the neurodegenerative process of Alzheimer's disease (AD) and to differentiate it from other brain diseases which may cause similar symptoms. Structural imaging can detect atrophic changes which are largely non-specific and provide little diagnostic information in single patients. Increasing atrophy upon repeated measurement is much more specific to AD. Functional imaging can demonstrate regional alterations of cerebral blood flow and metabolism but is not sufficiently sensitive at the stage of mild dementia. The measurement of neuronal proteins in the cerebrospinal fluid including tau, phospho-tau, and beta amyloid, achieve high diagnostic sensitivity and specificity even at the stage of pre-dementia. Genetic tests for mutations in the amyloid precursor and presenilin genes are applicable in very few cases. Apolipoprotein E genotyping is not useful as a diagnostic test. With respect to the limitations of biological markers clinical expertise will continue to be an essential element of the early and differential diagnosis of AD.