Markers of Alzheimer's Disease in Primary Visual Cortex in Normal Aging in Mice.

Aging is the principal risk factor for the development of Alzheimer's disease (AD). The hallmarks of AD are accumulation of the amyloid-ß peptide 1-42 (Aß42) and abnormal hyperphosphorylation of Tau (p-Tau) protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aß42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aß42, p-Tau, glial-acidic fibrillary protein (GFAP), and presenilin-2, one of the main enzymes involved in Aß42 production. Our results show a significant increase of Aß42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the visual cortex; they also show an increase of the expression of GFAP and presenilin-2 in this region. These results provide a comprehensive framework for the role of Aß42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging.

Oxidative stress caused by ozone exposure induces ß-amyloid 1-42 overproduction and mitochondrial accumulation by activating the amyloidogenic pathway.

Oxidative stress is a major risk factor for Alzheimer's disease (AD) that has been suggested to be the trigger of AD pathology. However, whether oxidative damage precedes and contributes directly to the intracellular accumulation of beta amyloid 1-42 (ßA42) peptide remains a matter of debate. Chronic exposure to low doses of ozone similar to the levels during a day of high pollution in México City causes a state of oxidative stress that elicits progressive neurodegeneration in the hippocampi of rats. Several reports have demonstrated that the mitochondria are among the first organelles to be affected by oxidative stress and ßA42 toxicity and act as sites of the accumulation of ßA42, which affects energy metabolism. However, the mechanisms related to the neurodegeneration process and organelle damage that occur in conditions of chronic exposure to low doses of ozone have not been demonstrated. To analyze the effect of chronic ozone chronic exposure on changes in the production and accumulation of the ßA42 and ßA40 peptides in the mitochondria of hippocampal neurons of rats exposed to ozone, we examined the mitochondrial expression levels of Presenilins 1 and 2 and ADAM10 to detect changes related to the oxidative stress caused by low doses of ozone (0.25ppm). The results revealed significant accumulations of ßA42 peptide in the mitochondrial fractions on days 60 and 90 of ozone exposure along with reductions in beta amyloid 1-40 accumulation, significant overexpressions of Pres2 and significant reductions in ADAM10 expression. Beta amyloid immunodetection revealed that there were some intracellular deposits of ßA42 and that ßA42 and the mitochondrial markers OPA1 and COX1 colocalized. These results indicate that the time of exposure to ozone and the accumulation of ßA42 in the mitochondria of the hippocampal cells of rats were correlated. Our results suggest that the accumulation of the ßA42 peptide may promote mitochondrial dysfunction due to its accumulation and overproduction.

PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach.

Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-ß peptides. 150 RNA samples from the entorhinal cortex, auditory cortex and hippocampal regions of individuals with Alzheimer's disease (AD) and controls elderly subjects were analyzed with using real-time rtPCR. There were no differences between groups for PSEN1 expression. PSEN2 was significantly downregulated in the auditory cortex of AD patients when compared to controls and when compared to other brain regions of the patients. Alteration in PSEN2 expression may be a risk factor for AD.