Alzheimer Disease: Davies HA

Simonsen AH, McGuire J, Hansson O, Zetterberg H, Podust VN, Davies HA, Waldemar G, Minthon L, Blennow K. · Biomarker Discovery Center Facility, Ciphergen Biosystems, Inc., 2100 Copenhagen O, Denmark. · Arch Neurol. · Pubmed #17353378 links to  free full text

Abstract: OBJECTIVE: To use proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides able to differentiate between patients with stable mild cognitive impairment (MCI) and those who will progress to Alzheimer disease (AD). DESIGN: Baseline cerebrospinal fluid samples from patients with MCI and healthy controls were profiled using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. SETTING: Memory disorder clinic. PARTICIPANTS: Patients with MCI (n = 113), of whom 56 were cognitively stable and 57 progressed to AD with dementia during a 4- to 6-year follow-up, as well as 28 healthy controls who were followed up for 3 years. Main Outcome Measure During follow-up, 57 patients progressed to AD and 56 patients had stable MCI. Cerebrospinal fluid from these 2 groups of patients was compared using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: We identified a panel of 17 potential biomarkers that could distinguish between patients with stable MCI and patients with MCI who progressed to AD. We have positively identified and characterized 5 of the potential biomarkers. CONCLUSIONS: Proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of MCI progression to AD. The 5 identified biomarkers are relevant to the pathogenesis of AD and could help gain an understanding of the molecular pathways in which they may function.

Simonsen AH, Hansson SF, Ruetschi U, McGuire J, Podust VN, Davies HA, Mehta P, Waldemar G, Zetterberg H, Andreasen N, Wallin A, Blennow K. · Biomarker Discovery Center Facility, Ciphergen, Copenhagen, Denmark. · Dement Geriatr Cogn Disord. · Pubmed #17310122 No free full text.

Abstract: BACKGROUND/AIMS: Amyloid beta (Abeta) is the principal component of senile plaques, one of the hallmarks of Alzheimer's disease (AD). Evidence is accumulating that soluble aggregates (oligomers) of Abeta are important in the pathogenesis of AD. METHODS: We compared three different methods for quantification of the 40 amino acid form of Abeta (Abeta40) in CSF, two based on antibodies [ELISA and surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) with antibody-coated arrays] and one based on direct binding of proteins to a protein array [SELDI-TOF and immobilized metal affinity [copper] (IMAC30)]. RESULTS: CSF Abeta40 concentration was only found to be significantly elevated in AD (127% of control levels; p=0.0095) using SELDI-TOF with IMAC30 arrays. CONCLUSIONS: These data suggest that the measured Abeta level in CSF may differ depending on whether antibody-based methods are used or not, possibly caused by epitope masking due to Abeta oligomerization or to binding of Abeta to carrier proteins.