CHROMOGRANIN-A IN CEREBROSPINAL-FLUID - A BIOCHEMICAL MARKER FOR SYNAPTIC DEGENERATION IN ALZHEIMERS-DISEASE

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase th e knowledge of the pathogenesis of the disorder. One of the main featu res of AD is a degeneration of synapses. Therefore, we examined if chr omogranin A (CrA), the major protein of large dense-core synaptic vesi cles, in cerebrospinal fluid (CSF) may be of value as a biochemical ma rker for the synaptic function in AD. The mean concentration of CrA in CSF was about 7.5 times higher than its concentration in serum, and t here was no significant correlation between CSF-CrA and the blood-brai n barrier function (measured as the CSF/serum albumin ratio), nor betw een CSF-CrA and serum-CrA. These findings suggest that the major porti on of CSF-CrA is locally produced within the CNS. There were no signif icant differences in CSF-CrA between the AD (n = 29), vascular dementi a (n = 13), and age-matched control (n = 9) groups (99.9 +/- 58.9 ng/m l, 108.0 +/- 69.4 ng/ml, and 115.1 +/- 44.4 ng/ml, respectively). Howe ver, when the AD group was subdivided into AD type I (n = 12) and AD t ype II (n = 17), a lower concentration of CSF-CrA was found in AD type I (72.8 +/- 28.9 ng/ml) compared with controls (115.1 +/- 44.4 ng/ml) , p < 0.02, and compared with AD type II (119.1 +/- 67.5 ng/ml), p < 0 .05, while CSF-CrA did not significantly differ between AD type II and controls. These findings suggest that CSF-CrA has a potential as a bi ochemical marker for the synaptic degeneration in AD type I, and gives further support for the relevance of identifying the AD type I (pure AD) subgroup in scientific studies.