Poster
# 118
Poster |
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6th Internet World Congress for Biomedical Sciences |
Domizio Suvā(1), Isabelle Favre(2), Rudolf Kraftsik(3), Monica Esteban(4), Alexander Lobrinus(5), Judit Miklossy(6)
(1)(2)(4)(5)(6)CHUV, Institute of Pathology - Lausanne. Switzerland
(3)IBCM - Lausanne. Switzerland
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[Neuroscience] |
[Pathology] |
It is generally accepted that the entorhinal cortex, hippocampus but also the frontal and parietal associative areas are severely involved in AD. The primary motor cortex is known to be less involved or even spared in AD (11,13-16,18,20,23,24,28). Based on these data, several authors have proposed that the distribution of plaques and tangles through the cerebral cortex may follow neuronal connections (12,17,19,22,26), and that the involvement of the associative cortical areas is correlated with their connections to the limbic areas.
Senile plaques are generally reported as being the most abundant in the associative neocortical areas, less numerous in entorhinal cortex and hippocampus, with the lowest density in the primary cortical areas (12,16,20,21). Neurofibrillary tangles are consistently reported as being very numerous in the entorhinal cortex, followed by hippocampus, the neocortical associative areas and finally the primary projection areas.
Severe involvement of the primary motor cortex in AD was only occasionally reported (29,30,35). Perretti (36) suggested, after obtaining abnormal electrophysiologic responses in abductor pollicis brevis and tibialis anterior muscles in AD patients using transcranial magnetic stimulation of the motor cortex, that sub-clinical dysfunction of the motor cortex neurons is present in AD before the clinical signs become apparent. Specific signs of pyramidal involvement, including Babinski sign, increased deep tendon reflexes and spasticity have been reported to occur in rare AD cases (29,30,37). Moreover, the occurrence of AD-type cortical changes in the primary motor cortex has been described in progressive supra-nuclear palsy and in amyotrophic lateral sclerosis (38,39).
Here, using a quantitative analysis, the primary motor cortex of 17 AD cases was analyzed for the occurrence of cortical AD-type changes. The great variation in size and shape of senile plaques for a same patient and from a patient to another (20,33) makes counting of plaques poorly reproducible. We therefore, we have chose to measure the percentage of cortical surface occupied by senile plaques. The results of the morphometric analysis showed that in all the 17 AD cases the primary motor cortex was severely affected. The percentage of cortical surface occupied by senile plaques was as high as in the other cortical areas, including the associative frontal and parietal areas. In a few AD cases the number of plaques and/or tangles was even higher in the primary motor cortex than in the entorhinal or associative cortical areas.
In agreement with the generally accepted view our quantitative analysis of neurofibrillary tangles showed that the most involved cortical region is the entorhinal cortex. The number of tangles was significantly lower in the associative cortical areas followed by the primary motor and primary sensory cortex. The difference between the number of tangles in associative areas and primary motor cortex showed only borderline significance.
In the majority of cases with discrete to moderate AD-type cortical changes, senile plaques were found in reduced number in all cortical areas including the primary motor cortex, suggesting an early appearance of plaques in the primary motor cortex. In one case with Braak stage IV a few neurofibrillary tangles were also present in the primary motor cortex.
In two AD cases the accumulation of plaques in the frontal cortex was much more severe than in the parietal cortex, indicating that regional variation of the severity of cortical changes may occur in AD.
The severity of the primary motor cortex involvement by senile plaques was strongly correlated with that of primary sensory, enthorhinal and frontal associative cortex. The correlation was also high between the number of neurofibrillary tangles the primary motor cortex and the sensory, parietal and frontal associative cortex.
The other primary cortical areas, the primary sensory and visual cortex were also involved in AD. There was a high correlation between the involvement of the primary motor and sensory cortex.
If we consider the histopathological criteria of AD following Khachaturian (8) or CERAD (9), where the diagnosis of AD depends particularly on the number of senile plaques, our results indicate that the involvement of the primary motor cortex is as severe as those of the frontal and parietal associative areas. However, if we consider the number of neurofibrillary tangles, which is even more significantly correlated with dementia severity (41), in spite of an important number of tangles in the primary motor cortex in all AD cases, their number is somewhat lower than in the associative areas. The distribution of neurofibrillary tangles suggest a progressive involvement of the cerebral cortex from the entorhinal cortex, hippocampus, through the associative cortical areas, to the primary motor and sensory cortical areas. Further analysis of the distribution of tangles in a high number of cases with discrete, moderate and severe AD-type cortical changes would be of interest to address this point more accurately.
In addition to the accumulation of plaques and tangles we have observed neuronal loss in all layers of the primary motor cortex, including those of the Betz cells in layer V/b. A quantitative analysis of neuronal loss in the primary motor cortex would add further information concerning the severity of the primary motor cortex involvement in AD.
Our results indicate the primary motor cortex is affected in AD and may well lead to severe motor dysfunctions in the late stages of the disease. In a prospective study, the neurological examination of motor functions followed by the neuropathological analysis of the primary motor cortex in AD patients would permit to define more accurately the clinical significance of the involvement of the primary motor cortex observed in this study.
Our findings suggest that AD affects not only the phylogenetically new and vulnerable associative brain regions and their connections (24). With the progression of the disease the primary motor cortex became also severely involved, suggesting that motor dysfunctions will appear in late and terminal stages of the disease.
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[Neuroscience] |
[Pathology] |
