Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected.
Numbers of neuropeptide Y (NPY) and parvalbumin (PV) immunoreactive (IR) cells were decreased in the hippocampus of 1 month-old TgCRND8 mouse AD model in a sub-regionally specific manner.
Numerous studies have indicated that the neuropeptides including ghrelin, neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y, substance P and orexin are closely related to the pathophysiology of Alzheimer's disease.
Finally, we recapitulate our recent in-vitro evidence for the involvement of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the neuroprotective effect elicited by NPY in AD neuron-like models (neuroblastoma cells or primary cultures exposed to toxic concentrations of Aβ's pathogenic fragment 25-35), and propose a putative mechanism based on NPY-induced inhibition of voltage-dependent Ca(2+) influx in pre- and post-synaptic neurons.
Since APOE varepsilon4 allele is also a major risk factor for the development of Alzheimer's disease (AD) and the genetic polymorphism of NPY has not previously been studied in dementing disorders, we have examined whether a novel polymorphism in a signal peptide of NPY gene is associated with AD alone or in combination with APOE varepsilon4.