Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.

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Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by dementia and the aggregation of the amyloid beta peptide (Aβ). Aβ25–35 is the most neurotoxic sequence, whose mechanism is associated with the neuronal death in the Cornu Ammonis 1 (CA1) region of the hippocampus (Hp) and cognitive damage. Likewise, there are mechanisms of neuronal survival regulated by heat shock proteins (HSPs). Studies indicate that pharmacological treatment with flavonoids reduces the prevalence of AD, particularly epicatechin (EC), which shows better antioxidant activity. The aim of this work was to evaluate the effect of EC on neurotoxicity that causes Aβ25–35 at the level of spatial memory as well as the relationship with immunoreactivity of HSPs in the CA1 region of the Hp of rats. Our results show that EC treatment reduces the deterioration of spatial memory induced by the Aβ25–35, in addition to reducing oxidative stress and inflammation in the Hp of the animals treated with EC + Aβ25–35. Likewise, the immunoreactivity to HSP-60, -70, and -90 is lower in the EC + Aβ25–35 group compared to the Aβ25–35 group, which coincides with a decrease of dead neurons in the CA1 region of the Hp. Our results suggest that EC reduces the neurotoxicity induced by Aβ25–35, as well as the HSP-60, -70, and -90 immunoreactivity and neuronal death in the CA1 region of the Hp of rats injected with Aβ25–35, which favors an improvement in the function of spatial memory.

Alzheimer's disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged synaptic structures called "Meganeurite clusters" have been linked to plasticity changes. The aims of this study were to determine if cognitive impairment was related to specific neuritic and synaptic degeneration processes in patients with AD, and if the results of a cognitive test could be correlated with the histopathological damage. The neuropsychological evaluation obtained by the Protocole d'evaluation neuropsychologique optimal (PENO) test battery was used in live AD and control individuals. The histopathological evaluation of their brain after their death was carried out with specific polyclonal and monoclonal antibodies to Aβ, pTau protein, synaptophysin, and GAP-43. Images were obtained by confocal microscopy. The results showed a significant difference between healthy controls and Alzheimer's patients in neuropsychological evaluation and histopathological hallmarks expression. The most significant positive correlation in AD patients was between memory and language results with the PENO test and the presence of Aβ +pTau+ plaques in the hippocampus. An interesting negative correlation was between cognitive impairment and the presence of Meganeuritic clusters, considered as "plasticity" markers. These results strongly supported the use of the PENO battery test to evaluate the progression of cogni-* Corresponding author. R. Karla et al. 240 tive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer's disease.