6.9. INVOLVEMENT OF OLFACTORY SYSTEM AS THE EARLIEST EVENT IN ALZHEIMER'S DISEASE
One portal of entry for oral spirochetes would be the olfactory tract and bulb. If these spirochetes are involved in AD, the involvement of olfactory system should be one of the earliest events in AD .
Oral spirochetes may invade the CNS via the olfactory system. If oral spirochetes may play a role in AD, (Miklossy, 1993; Riviere et al., 2002) we anticipated that the olfactory system may be affected in early stages of AD. The analysis of 110 autopsy cases showed a close association between the cortical and olfactory AD-type changes and indicated that the involvement of the olfactory bulb and tract is indeed one of the earliest events in the degenerative process of AD (Christen-Zaech et al., 2003).
BACKGROUND: In Alzheimer's disease (AD) the olfactory system, including the olfactory bulb, a limbic paleocortex is severely damaged. The occurrence of early olfactory deficits and the presence of senile plaques and neurofibrillary tangles in olfactory bulb were reported previously by a few authors. The goal of the present study was to analyze the occurrence of AD-type degenerative changes in the peripheral part of the olfactory system and to answer the question whether the frequency and severity of changes in the olfactory bulb and tract are associated with those of the cerebral cortex in AD.
MATERIAL AND METHODS: In 110 autopsy cases several cortical areas and the olfactory bulb and tract were analyzed using histo- and immunohistochemical techniques. Based on a semiquantitative analysis of cortical senile plaques, neurofibrillary tangles and curly fibers, the 110 cases were divided into four groups: 19 cases with severe (definite AD), 14 cases with moderate, 58 cases with discrete and 19 control cases without AD-type cortical changes.
RESULTS: The number of cases with olfactory involvement was very high, more than 84% in the three groups with cortical AD-type lesions. Degenerative olfactory changes were present in all 19 definite AD cases, and in two of the 19 controls. The statistical analysis showed a significant association between the peripheral olfactory and cortical degenerative changes with respect to their frequency and severity (P < 0.001). Neurofibrillary tangles and neuropil threads appear in the olfactory system as early as in entorhinal cortex.
CONCLUSION: The results indicate a close relationship between the olfactory and cortical degenerative changes and indicate that the involvement of the olfactory bulb and tract is one of the earliest events in the degenerative process of the central nervous system in AD.