Biomarkers for Early Detection of Alzheimer¡¯s

New studies have identified multiple biomarkers and biomarker patterns that may lead to early detection of Alzheimer¡¯s disease (AD) and suggest new targets for therapy. The results were presented at the 9th International Conference on Alzheimer¡¯s Disease in Philadelphia (PA, USA) in July 2004.

Among the presenters was Prof. Kaj Blennow, M.D., Ph.D., from the University of Gothenburg (Sweden), who reported promising data from a recent study conducted in collaboration with the diagnostics division of Ciphergen Biosystems, Inc. (Fremont, CA, USA). Dr. Blennow noted that early diagnosis of AD is of importance for the initiation of symptomatic treatment with acetyl cholinesterase (AChE) inhibitors, and will be of even greater significance if drugs aimed at slowing the degenerative process, such as vaccination regimes and ©¬- and ¥ã-secretase inhibitors, prove to have clinical effect.

In the study, researchers found that if put in the right clinical context, the cerebral spinal fluid (CSF) biomarkers tau (T-tau), phospho tau (P-tau), and A©¬42 have high diagnostic accuracy to identify AD and to differentiate AD from normal aging and several important differential diagnoses. These CSF biomarkers can also help clinicians to determine which of the patients with mild cognitive impairment (MCI) will progress to AD and which have a benign form of MCI.

However, the specificity against other dementias was not optimal. A better way may be to use a larger panel of biomarkers for different pathogenic processes. The researchers developed multi-immunoassays using the Luminex xMAP technology. The first assay for simultaneous measurement T-pau, P-tau181, and A©¬42 showed high analytical precision and diagnostic performance. Simultaneous measurement of several N-terminally truncated A©¬42 variants improved the performance to identify MCI cases with incipient AD.

Different proteomic approaches were used in the search for new CSF markers for AD. Researchers used the ProteinChip SELDI-TOF (surface-enhanced laser desorption ionization-time of flight) technology developed by Ciphergen in the search for a specific AD biomarker pattern. In their first study using this technique, they found an increase in 36 and a decrease in 16 peptides/proteins in AD. After data processing, five peaks showed a sensitivity of 100% for AD at a specificity level of 91%. The SELDI-TOF technique can also be used to characterize changes in the isoform pattern of specific proteins and peptides, such as truncated ©¬-amyloid variants.

CSF biomarkers may also be valuable tools to identify and monitor a biochemical effect of new treatment regimes in living patients, noted the researchers. The CSF level of AChE showed a dose-dependent change during treatment with AChE inhibitors that also correleated to clinical outcome.

¡°Ciphergen has made significant progress working with leading researchers to develop a potential multimarker SELDI-based assay for the diagnosis of AD that utilizes novel biomarkers,¡± confirmed Huw Davies, Ph.D., manager of Ciphergen¡¯s European Biomarker Center.




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