**5. Endoplasmic reticulum (ER) stress response and histopathological changes in Alzheimer's disease**

Alzheimer's disease is the most common type of dementia. It is a progressive disease that begins with mild memory loss, possibly leading to loss of the ability to maintain speech and react to the environment [51]. Alzheimer's disease involves parts of the brain that control thought, memory, and language. As a result of studies on Alzheimer's, he stated that ER stress plays a vital role in the pathogenesis of Alzheimer's [52, 53]. Some studies determined that Ca homeostasis and accumulation of phosphorylated tau protein and intracellular amyloid-β play an important role in this disease. Again, some studies have shown that pPERK, pIRE1, and elF2α, which are the kinases of the UPR, are increased in the hippocampus and brain tissue neurons of Alzheimer's patients [54]. Again, PERK, eIF2α, and p38 MAPK activation associated with the presence of tau protein were observed in Alzheimer's patients. These findings clearly demonstrated the relationship between tau proteins in neurons and ER stress. In some studies, it has been stated that Alzheimer's disease increases as a result of cerebral ischemia or stroke. This is a clear indication that aging impairs the folded protein response by disrupting ER homeostasis due to oxidative stress and plays a role in the pathogenesis of the disease. Some studies on the UPR have reported increased levels of BIP/GRP78, protein kinase, and PERK in the brain of Alzheimer's patients [55].

*The Relationship of Some Neurodegenerative Diseases with Endoplasmic Reticulum Stress… DOI: http://dx.doi.org/10.5772/intechopen.111693*

The ER stress-mediated inflammatory response has an important role in Alzheimer's disease pathogenesis. The inflammatory response is normally triggered by the activation of inflammatory receptors, including TLRs (toll-like receptors) and NLRs (NOD-like receptors). These pattern recognition receptors transduce the signaling mostly via the NF-κB pathway and trigger the inflammatory response [56]. Additionally, the ER stress-mediated inflammatory response has a role in the pathogenesis of some diseases [57]. In obesity, ER stress can induce an inflammatory response and cause peripheral insulin resistance [58], and in the liver, ER stress can trigger the systemic inflammatory response and cause damage [59]. In neurodegenerative diseases, inflammatory processes are initiated by the maturation of the IL-1 cytokines called as inflammasomes [60].

Histopathologically senile amyloid in Alzheimer's disease plaques (SAP), neurofibrillary flock (NF) formation, loss of synapsneurons, and marked atrophy in the brain are detected [51]. The formation of senile plaques is the most important histopathological finding of the disease. It is a symptom of the disease and is seen especially in the amygdala, hippocampus, and neocortex. On the other hand, NF is required for the definitive diagnosis of AD [52]. And the detection of SPs is necessary but not sufficient. Both lesions occur both in normal aging and in some and can be seen in other neurodegenerative diseases. AD for the definitive diagnosis of NFY and SAP is a certain neuroanatomical. They must be shown to be in the distribution and in certain quantities [53].
