IMR Press / JIN / Volume 20 / Issue 4 / DOI: 10.31083/j.jin2004107
Open Access Review
Vasoactive neuropeptides and Alzheimer’s disease: a systematic review focusing on calcitonin gene-related peptide
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1 Neurology Clinic, Azienda Ospedaliero Universitaria, Ospedali Riuniti di Ancona, 60126 Ancona, Italy
2 Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy
3 Radiology Department, Azienda Ospedaliero Universitaria, Ospedali Riuniti di Ancona, 60126 Ancona, Italy
4 Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, 60126 Ancona, Italy
J. Integr. Neurosci. 2021, 20(4), 1059–1065;
Submitted: 2 September 2021 | Revised: 15 September 2021 | Accepted: 27 October 2021 | Published: 30 December 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

Vasoactive peptides constitute a heterogenous family of mediators exerting various physiological functions, mostly studied for their vasotropic effects and role as peripheral neurotransmitters/neuromodulators, mainly involved in nociceptive transmission modulation. They have been divided into vasodilatory or vasoconstrictive peptides, according to their predominant effects on vascular tone. Recent research has shown in the Central Nervous System effects as transmitters and “growth factor-like” signals. Therefore, deregulation of their signaling systems has been thought to play a role in neural cell death and in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease, since these peptides can regulate neuronal stress signaling, survival cascades, synaptic plasticity. This review considers evidence about the implication of neuropeptide systems in Alzheimer’s disease while focusing mainly on calcitonin gene-related peptide-alpha. In vitro and in vivo studies have shown potential implications in its pathogenesis. It has been possibly proposed as a neuroprotective agent, considering not only its pleiotropic actions on blood vessels, neurovascular coupling, energy metabolism, but also its potential actions on neuronal, glial, and immune system stress signaling, which might also derive from its structural homology to amylin. Amylin signaling is thought to be disrupted in Alzheimer’s disease, and amylin itself takes part in the composition of senile plaques. Calcitonin gene-related peptide-containing systems seem more closely related to Alzheimer’s disease pathogenesis than other neuropeptidergic systems, and their regulation might represent an interesting mechanism in developing novel therapeutic approaches.

Calcitonin gene-related peptide
Vasodilatory peptides
Vasoconstrictive peptides
Alzheimer's disease
Fig. 1.
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