title: Cerebrospinal fluid levels of Aβ42 relationship with cholinergic cortical activity in Alzheimer's disease patients.
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.
authors.affiliation: Dipartimento di Neuroscienze, Università di Roma TorVergata, Viale Oxford 81, 00133, Rome, Italy. martorana@med.uniroma2.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Zaira
authors.initials: Z
authors.lastname: Esposito
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Lorenzo
authors.forename: Viola
authors.initials: V
authors.lastname: Giacobbe
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: Sancesario
authors.forename: Giulia
authors.initials: G
authors.lastname: Bucchi
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonnì
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorge
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancesario
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Giacomo
authors.initials: G
authors.lastname: Koch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D059329:Cholinergic Neurons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins