Nhiều vấn đề chưa được giải quyết tiếp tục với bệnh dịch hạch sự hiểu biết của chúng ta về sinh bệnh học của AD. Mặc dù biết rằng cái chết của tế bào thần kinh có thể xảy ra do NFT hình thành và bệnh mạch máu não | ALZHEIMER S DISEASE 187 Unresolved Issues Fig. 4. Many unresolved issues continue to plague our understanding of the pathogenesis of AD. Although it is known that neuronal death can occur due to NFT formation and cerebrovascular disease such as cerebral amyloid angiopathy CAA altered perfusion or mi-crovascular pathology pale arrows the exact role of Afi and inflammation are unknown dark arrows . Aft deposition and inflammation are both universal findings in the brain of AD and the former is necessary for a pathological diagnosis of AD. However whether either results in neuronal death and if so by what mechanism is yet to be determined. major mechanism of neuronal degeneration occurs in AD. Unfortunately the lack of a readily identifiable marker for this neuronal loss has made the identification of its cause extremely difficult. A study has shown that the prolyl isomerase Pinl is sequestered into the NFT and depleted in the brains of AD patients Lu et al. 1999 . 188 JILLIAN J. KRIL AND GLENDA M. HALLIDAY Depletion of Pinl may induce neuron death via mitotic arrest and apoptosis prior to the development of NFTs Lu et al. 1996 . The neuron-specific activator for cell proteins involved in the mitotic cycle is p35 which is pro-teolytically cleaved to produce p25 a fragment found to accumulate in the brains of patients with AD Patrick et al. 1999 . Application of A Ỉ1-42 induces the conversion of p35 to p25 Lee et al. 2000 . p25 links with cell cycle-dependent kinase 5 to hyperphosphorylate tau and promote apoptosis Lee et al. 2000 . Degenerating neurons in APP V717F A 3-producing transgenic mice show chromatin segmentation and condensation as well as increased TUNEL staining suggestive of apoptosis Nijhawan et al. 2000 . This supports a link between Aft deposition and apoptosis Fig. 4 . Increased TUNEL staining Druganow et al. 1995 Lassmann et al. 1995 Smale et al. 1995 Bancher et al. 1997 as well as cleaved caspase 3 Selznick et al. 1999 Stadelmann et al. 1999 an .
