Cerebrospinal fluid levels of Aβ42 relationship with cholinergic cortical activity in Alzheimer's disease patients

Alessandro Martorana, Zaira Esposito, Francesco Di Lorenzo, Viola Giacobbe, Giulia Maria Sancesario, Giulia Bucchi, Sonia Bonnì, Sergio Bernardini, Roberto Sorge, Giuseppe Sancesario, Giorgio Bernardi, Carlo Caltagirone, Giacomo Koch

Research output: Contribution to journalArticle

Abstract

The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). In animal models of AD, fragments of amyloid beta protein (Aβ) and Tau protein are thought to interfere with central cholinergic transmission, specifically with synthesis and release of acetylcholine. Thus, we aimed to investigate whether the cerebrospinal fluid (CSF) levels of Aβ42 and Tau proteins in AD patients could influence physiological central cholinergic activity. In AD patients (n = 19), central cholinergic function was evaluated in vivo by using short afferent latency inhibition (SLAI), and compared to age-matched healthy controls. In the same AD patients, CSF samples were collected through lumbar puncture to obtain individual levels of Aβ42, total Tau (t-Tau) and phosphorylated Tau (p-Tau) (Thr181). SLAI was decreased in AD patients in comparison to age-matched healthy controls. We found that in patients there was a negative correlation between the individual amount of cholinergic activity assessed by SLAI and the CSF levels of Aβ42. On the other hand, there was a positive correlation between the levels of SLAI and CSF p-Tau. No correlation was found when SLAI was analysed together with t-Tau. These results demonstrate that mechanisms of cortical cholinergic activity are altered in patients bearing a pathological CSF hallmark of AD, suggesting that these peptides may have some influence on the cholinergic dysfunction in AD. We suggest that coupling of CSF biomarkers with neurophysiological parameters of central cholinergic function could be important to better detect ongoing mechanisms of neural degeneration in vivo.

Original languageEnglish
Pages (from-to)771-778
Number of pages8
JournalJournal of Neural Transmission
Volume119
Issue number7
DOIs
Publication statusPublished - Jul 2012

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Keywords

  • Aβ42
  • Alzheimer's disease
  • Cerebrospinal fluid
  • SLAI
  • TMS

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Martorana, A., Esposito, Z., Di Lorenzo, F., Giacobbe, V., Sancesario, G. M., Bucchi, G., Bonnì, S., Bernardini, S., Sorge, R., Sancesario, G., Bernardi, G., Caltagirone, C., & Koch, G. (2012). Cerebrospinal fluid levels of Aβ42 relationship with cholinergic cortical activity in Alzheimer's disease patients. Journal of Neural Transmission, 119(7), 771-778. https://doi.org/10.1007/s00702-012-0780-4