Aβ1–42 Detection in CSF of Alzheimer's disease is influenced by temperature: Indication of reversible Aβ1–42 aggregation?
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- 作者：Giulia M. Sancesario ; Zaira Esposito ; Marzia Nuccetelli ; Sergio Bernardini ; Roberto Sorge ; Aless ; ro Martorana ; Giorgio Federici ; Giorgio Bernardi ; Giuseppe Sancesario
- 关键词：Cerebrospinal fluid ; Biological marker ; Dementia ; Alzheimer's disease ; Oligomers
- 刊名：Experimental Neurology
- 出版年：2010
- 出版时间：June 2010
- 年：2010
- 卷：223
- 期：2
- 页码：371-376
- 全文大小：220 K
文摘
Amyloid-beta 1–42 (Aβ1–42), peptide detectable in cerebrospinal fluid (CSF), has been extensively studied as diagnostic marker for Alzheimer's disease; however, results are variable. We investigated whether Aβ1–42 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 °C, or handled according to standard procedures and centrifuged at 4 °C for 10 min; thereafter, one aliquot was further stored at 4 °C and another at 37 °C, before freezing all samples 90 min later at − 80 °C, pending analysis. Aβ1–42 and total tau were determined using a commercially available sandwich enzyme-linked immunosorbent assay ELISA. Reduced Aβ1–42 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 °C before freezing. However, avoiding cooling or reheating CSF from 4 to 37 °C before freezing strikingly increased the Aβ1–42 concentration detectable in the AD group (P < 0.01), but not in control groups. The results indicate that a pool of Aβ1–42 cannot be detectable in the CSF of AD patients, because standard preanalytical cooling masks in some ways the epitope recognized by Aβ1–42 specific antibodies. Moreover, our study suggests that low temperature could induce Aβ1–42 conformational changes and multimeric aggregates in probable AD, but, more importantly, Aβ1–42 aggregation could be reversible.