Neuropeptides are small proteins broadly expressed throughout the central nervous system,
which act as neurotransmitters, neuromodulators and neuroregulators. Growing evidence has demonstrated
the involvement of many neuropeptides in both neurophysiological functions and neuropathological
conditions, among which is Alzheimer’s disease (AD). The role exerted by neuropeptides in
AD is endorsed by the evidence that they are mainly neuroprotective and widely distributed in brain
areas responsible for learning and memory processes. Confirming this point, it has been demonstrated
that numerous neuropeptide-containing neurons are pathologically altered in brain areas of both AD
patients and AD animal models. Furthermore, the levels of various neuropeptides have been found
altered in both Cerebrospinal Fluid (CSF) and blood of AD patients, getting insights into their potential
role in the pathophysiology of AD and offering the possibility to identify novel additional biomarkers
for this pathology. We summarized the available information about brain distribution, neuroprotective
and cognitive functions of some neuropeptides involved in AD. The main focus of the current review
was directed towards the description of clinical data reporting alterations in neuropeptides content in
both AD patients and AD pre-clinical animal models. In particular, we explored the involvement in the
AD of Thyrotropin-Releasing Hormone (TRH), Cocaine- and Amphetamine-Regulated Transcript
(CART), Cholecystokinin (CCK), bradykinin and chromogranin/secretogranin family, discussing their
potential role as a biomarker or therapeutic target, leaving the dissertation of other neuropeptides to
previous reviews.