Muscarinic Receptors Expression in the Peripheral Blood Cells Differentiate Dementia with Lewy Bodies from Alzheimer’s Disease

Article type: Research Article

Authors: Reale, Marcella^a | Carrarini, Claudia^b | Russo, Mirella^b | Dono, Fedele^b | Ferri, Laura^b | Di Pietro, Martina^b | Costantini, Erica^c | Porreca, Annamaria^d | Di Nicola, Marta^d | Onofrj, Marco^b | Bonanni, Laura^{c; *}

Affiliations: [a] Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy | [b] Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy | [c] Department of Medicine and Aging Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy | [d] Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy

Correspondence: [*] Correspondence to: Prof. Laura Bonanni, Department of Medicine and Aging Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy. Tel.: +39 0871 358525; E-mail: [email protected].

Abstract: Background:Central nervous system disruption of cholinergic (ACh) signaling, which plays a major role in cognitive processes, is well documented in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The expression of muscarinic ACh receptors type 1 and 4 (CHRM1 and CHRM4) has been reported to be altered in the brain of DLB patients. Objective:We aim to assess the peripheral gene expression of CHRM1 and 4 in DLB as a possible marker as compared to AD and healthy control (HC) subjects. Methods:Peripheral blood mononuclear cells were collected from 21 DLB, 13 AD, and 8 HC matched subjects. RT-PCR was performed to estimate gene expression of CHRM1 and CHRM4. Results:Peripheral CHRM1 expression was higher and CHRM4 was lower in DLB and AD compared to HC, whereas both CHRM1 and CHRM4 levels were higher in AD compared to DLB patients. Receiver operating characteristics curves, with logistic regression analysis, showed that combining peripheral CHRM1 and CHRM4 levels, DLB and AD subjects were classified with an accuracy of 76.0%. Conclusion:Alterations of peripheral CHRM1 and CHRM4 was found in both AD and DLB patients as compared to HC. CHRM1 and CHRM4 gene expression resulted to be lower in DLB patients compared to AD. In the future, peripheral CHRM expression could be studied as a possible marker of neurodegenerative conditions associated with cholinergic deficit and a possible marker of response to acetylcholinesterase inhibitors.

Keywords: Alzheimer’s disease, cholinergic imbalance, dementia with Lewy bodies, muscarinic receptors, real time-polymerase chain reaction

DOI: 10.3233/JAD-215285

Journal: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 323-330, 2022