Alzheimer's Disease and Apoptosis

Apoptosis is a form of cell death in which the cells shrink and exhibit nuclear chromatin condensation and DNA fragmentation, and yet maintain membrane integrity. Many lines of evidence have shown that brain neurons are vulnerable to degeneration by apoptosis. Also it has been suggested that apoptosis is one of the mechanism contributing neuronal loss in Alzheimer's disease(AD), since the conditions in the disease(A beta peptide, oxidative stress, low energy metabolism) are the inducers that activate apoptosis. Indeed some neurons in vulnerable regions of the AD brain show DNA damage, chromatin condensation, and apoptic bodies. Consistently, mutations in AD causative genes(Amyloid precursor protein, Presenilin-1 and Presenilin-2) increase A beta peptide1-42(Abeta1-42) and sensitize neuronal cell to apoposis. However, several lines of evidence have shown that the location of neuronal loss and A beta peptide deposition is not correlated in AD brain and transgenic mice brain over-expressing Abeta1-42. Taken together, these data may indicated that A beta peptide(and other causative factors of AD) can interact with other cellular insults or risk factors to exacerbate pathological mechansim of AD through apoptosis. Thus, this review discusses possible role and mechanism of apoptosis in AD.

Effect of Immobilization Stress on the Expression of Amyloid Precursor Protein in the Mouse Brain

BACKGROUND: The Central nervous system(CNS) plays a essential role in mediating~stress responses. However, the enact mechanism of the CNS in mediating stress responses has not been clarified sufficiently as yet. Stress may cause brain dysfunction including cognitive dysfunction which was most commonly found in Alzheimer's dementia. Amyloid precursor protein(APP) is a large, ubiquitously distributed and evolutionarily conserved molecule whose function remains unknown. Although the precise function of APP following injury to the CNS such as stab and kainic acid lesion. However, there have not been reports on the effects of stress on the expression of amyloid precursor protein in the brain. This study was undertaken to elucidate the effects of stress on the expression of APP in the mouse brain. METHODS: The several brain region was isolated from the mouse that was in the immoblization stress for 30 min, 1 hour, and 2 hours. The mouse brain was divided into 5 regions, cerebral cortex, cerebellum hippocampus, midbrain and thalamus, corpus striatum and brain stem. The change of mRNA was examined in the several brain regions using Northern blot hybridization. RESULTS: The amounts of APP mRNA in the cerebral cortex, hippocampus and brain stem were found to be significantly increased after stress for 30 minutes and to 1.each a maximum after stress for 1 hour and to normal range at stress for 2 hours. On the contray, the contents of APP mRNA in midbrain and thalamus were decreased after stress for 30 minutes and sustained after stress for 2 hours. CONCLUSION: These findings suggest that APP may not be static but functional protein reactive to stress and stress may increase the levels of APP mRNA especially in Alzheimer disease associated sites such as cerebral cortex and hippocampus, which may contriute to the pathogenesis of Alzheimer disease.