COMBINATION OF THE DIFFERENT BIOLOGICAL MARKERS FOR INCREASING SPECIFICITY OF IN-VIVO ALZHEIMERS TESTING

In view of existing drugs (acetylcholine esterase inhibitors) and emer ging therapeutic compounds (e.g. neuroprotective and antiinflammatory compounds), CSF markers would be of great use to improve the clinical diagnostic accuracy of Alzheimer's disease (AD). Correct identificatio n of AD would be especially important early in the course of the disea se, when the clinical diagnosis is difficult, and drugs have the great est potential of being effective. Biochemical markers for AD include A poE genotyping, where the ApoE epsilon 4 allele has proven to have a h igh predictive value for AD. Biochemical markers for AD also include s everal potential cerebrospinal fluid (CSF) markers: beta-amyloid((1-42 )), possibly reflecting amyloid deposition and formation of senile pla ques; PHFtau protein a marker for the phosphorylation state of tau, an d formation of neurofibrillary tangles; (total)tau protein, a normal a xonal protein, as a marker for ongoing neuronal and axonal degeneratio n; synaptic vesicle proteins, e.g. synaptotagmin, a synaptic vesicle p rotein which is found in the CSF, as markers for synaptic activity or degeneration; neuromodulin or growth-associated protein GAP-43, as a m arker for synaptic degeneration, and the CSF/serum albumin ratio, as a marker for blood-brain barrier damage, used to exclude patients with concomitant cerebrovascular pathology. However, although CSF markers m ay identify different pathogenic processes in AD, there is no such pro cess that is specific for AD, and thus little hope of ever finding a s ingle CSF biochemical marker that gives an absolute discrimination bet ween AD and other dementia disorders. Instead, combination of several CSF biochemical markers, each reflecting a pathogenic process, may inc rease both the sensitivity and specificity. Further, the accuracy of t he clinical diagnosis of AD may increase if the diagnosis is based on the summarised information gained from the clinical examination, brain -imaging techniques (SPECT, CT/MRT scans), and biochemical markers. Us ing this approach, CSF markers have a large potential to help to diffe rentiate AD from the most problematic differential diagnoses, especial ly age-associated memory impairment, depressive pseudo-dementia, Parki nson's disease, and frontal lobe dementia.