A beta 1-42 Detection in CSF of Alzheimer's disease is influenced by temperature: Indication of reversible A beta 1-42 aggregation?

作者：Sancesario Giulia M; Esposito Zaira; Nuccetelli Marzia; Bernardini Sergio; Sorge Roberto; Martorana Alessandro; Federici Giorgio; Bernardi Giorgio; Sancesario Giuseppe

来源：Experimental Neurology, 2010, 223(2): 371-376.

DOI：10.1016/j.expneurol.2009.07.028

• Cerebrospinal fluid
• Biological marker
• Dementia
• Alzheimer's disease
• Oligomers

Amyloid-beta 1-42 (A beta 1-42), peptide detectable in cerebrospinal fluid (CSF), has been extensively studied as diagnostic marker for Alzheimer's disease; however, results are variable. We investigated whether A beta 1-42 detection in CSF may be affected by handling temperature after lumbar puncture. CSF was collected from patients affected by probable AD (n=27), other dementias (OD) (n=24), or other neurological disorders without cognitive impairment (OND) (n=23). After lumbar puncture, CSF samples were either maintained at 37 degrees C, or handled according to standard procedures and centrifuged at 4 degrees C for 10 min; thereafter, one aliquot was further stored at 4 degrees C and another at 37 degrees C, before freezing all samples 90 min later at -80 degrees C, pending analysis. A beta 1-42 and total tau were determined using a commercially available sandwich enzyme-linked immunosorbent assay ELISA. Reduced A beta 1-42 and increased total tau CSF levels were confirmed as characteristic hallmarks of the OD and AD groups, providing standard measurement in samples stored at 4 degrees C before freezing. However, avoiding cooling or reheating CSF from 4 to 37 degrees C before freezing strikingly increased the A beta 1-42 concentration detectable in the AD group (P<0.01), but not in control groups. The results indicate that a pool of A beta 1-42 cannot be detectable in the CSF of AD patients, because standard preanalytical cooling masks in some ways the epitope recognized by A beta 1-42 specific antibodies. Moreover, our study suggests that low temperature could induce A beta 1-42 conformational changes and multimeric aggregates in probable AD, but, more importantly, A beta 1-42 aggregation could be reversible.

• 出版日期2010-6