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Early Olfactory Involvement in Alzheimer’s Disease

Published online by Cambridge University Press:  02 December 2014

S. Christen-Zaech
Affiliation:
University Institute of Pathology
R. Kraftsik
Affiliation:
1011, CHUV, Lausanne, Switzerland, Institute of Cellular Biology and Morphology
O. Pillevuit
Affiliation:
Division of Neuropathology, 1011, CHUV, Lausanne, Switzerland, Department of Oto-Rhino-Laryngology, Head and Neck Surgery
M. Kiraly
Affiliation:
University of Lausanne, 1005 Lausanne, Switzerland, Institute of Physiology
R. Martins
Affiliation:
University of Lausanne, 1005 Lausanne, Switzerland, University Department of Surgery
K. Khalili
Affiliation:
Hollywood Private Hospital, Nedlands, Perth 6009, Western Australia, and Center for Neurovirolgy and Cancer Biology, Temple University, Philadelphia, USA
J. Miklossy
Affiliation:
University Institute of Pathology Hollywood Private Hospital, Nedlands, Perth 6009, Western Australia, and Center for Neurovirolgy and Cancer Biology, Temple University, Philadelphia, USA
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Abstract

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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.

Résumé:

RÉSUMÉ: Contexte:

Le système olfactif incluant le bulbe olfactif, qui fait partie du paléocortex limbique, est sévèrement atteint dans la maladie d’Alzheimer (MA). L’existence d’un déficit olfactif précoce et la présence de plaques séniles et d’amas neurofibrillaires dans le bulbe olfactif ont été rapportés par quelques auteurs. Le but de cette étude était d’analyser les changements dégénératifs de type MA en périphérie du système olfactif et de déterminer si la fréquence et la sévérité des changements dans le bulbe et le pédoncule olfactif sont associées à ceux observés dans le cortex cérébral dans la MA.

Matériel et méthodes:

Plusieurs zones corticales ainsi que le bulbe et le pédoncule olfactif ont été analysés au moyen de techniques d’histo et d’immunohistochimie chez 110 cas d’autopsie. Les 110 cas ont été divisés en quatre groupes, selon une analyse semi-quantitative des plaques séniles corticales, des amas neurofibrillaires et des fibres incurvées: 19 cas atteints de changements corticaux de type MA sévères (MA certaine), 14 cas de changements modérés, 58 cas de changements discrets et 19 témoins sans changements.

Résultats:

Le nombre de cas avec atteinte olfactive était très élevé, soit plus de 84% dans les trois groupes de cas ayant des lésions de type MA. Des changements olfactifs dégénératifs étaient présents chez les 19 cas de MA certaine et chez deux des 19 témoins. L’analyse statistique a montré une association significative entre les changements dégénératifs olfactifs et corticaux quant à leur fréquence et à leur sévérité (P < 0,001). Les amas neurofibrillaires et de fibres tortueuses apparaissent dans le système olfactif aussi précocement que dans le cortex entorhinal.

Conclusions:

Ces résultats indiquent qu’il existe une relation étroite entre les changements dégénératifs olfactifs et corticaux et que l’atteinte du bulbe et du pédoncule olfactif est un des événements les plus précoces dans le processus dégénératif au niveau du système nerveux central dans la MA.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2003

References

1. Esiri, MM, Wilcock, GK. The olfactory bulbs in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1984; 47: 5660.Google Scholar
2. Davies, DC, Brooks, JW, Lewis, DA. Axonal loss from the olfactory tracts in Alzheimer’s disease. Neurobiol Aging 1993; 14: 353357.Google Scholar
3. Talamo, BR, Rudel, R, Kosik, KS, et al. Pathological changes in Alzheimer’s disease. Nature 1989; 337: 736739.CrossRefGoogle Scholar
4. Utsumi, M, Sato, K, Tanimukai, H, et al. Presenilin-1 mRNA and b amyloid precursor protein mRNA are expressed in the developing rat olfactory and vestibulocochlear systems. Acta Otolaryngol 1998; 118: 549553.Google Scholar
5. Fonte, J, Miklossy, J, Atwood, C, Martins, R. The severity of cortical Alzheimer’s type changes is positively correlated with increased amyloid-blevels: resolubilization of amyloid-bwith transition metal ion chelators. J Alzheimer Dis 2001; 3: 209219.Google Scholar
6. Khachaturian, ZS. Diagnosis of Alzheimer’s disease. Arch Neurol 1985; 42: 10971105.Google Scholar
7. Kovacs, T, Cairns, NJ, Lantos, PL. b-Amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer’s disease. Neuropathol Appl Neurobiol 1999; 25: 481491.Google Scholar
8. Murphy, C, Gilmore, MM, Seery, CS, Salmon, DP, Laskar, BR. Olfactory thresholds are associated with degree of dementia in Alzheimer’s disease. Neurobiol Aging 1990; 11: 465469.Google Scholar
9. Kwok, JB, Taddei, K, Hallupp, M, et al. Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer’s disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype. Neuroreport 1997; 8: 15371542.CrossRefGoogle ScholarPubMed
10. Miklossy, J, Kraftsik, R, Pillevuit, O, et al. Curly fiber and tangle-like inclusions in the ependyma and choroid plexus- a pathogenetic relationship with the cortical Alzheimer-type changes? J Neuropathol Exp Neurol 1998; 57: 12021212.Google Scholar
11. Hyman, BT, Arriagada, PV, Van Hoesen, GW. Pathologic changes in the olfactory system in aging and Alzheimer’s disease. Ann N Y Acad Sci 1991; 640: 1419.Google Scholar
12. Doty, RL. Olfactory capacities in aging and Alzheimer’s disease. Psychophysical and anatomic considerations. Ann N Y Acad Sci 1991; 40: 2027.Google Scholar
13. Rogers, J, Morrison, JH. Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer’s disease. J Neurosci 1985; 5: 28012808.Google Scholar
14. Mann, DM, Tucker, CM, Yates, PO. Alzheimer’s disease: an olfactory connection? Mech Aging Develop 1988; 42: 115.Google Scholar
15. Pearson, RCA, Esiri, MM, Hiorns, RW, Wilcock, GK, Powell, TPS. Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer’s disease. Proc Natl Acad Sci 1985; 82: 45314534.CrossRefGoogle Scholar
16. Ohm, TG, Braak, E. Olfactory bulb changes in Alzheimer’s disease. Acta Neuropathol 1987; 73: 365369.CrossRefGoogle ScholarPubMed
17. Doty, RL, Reyes, PF, Gregor, T. Presence of both odour identification and detection deficits in Alzheimer’s disease. Brain Res Bull 1987; 18: 597600.CrossRefGoogle ScholarPubMed
18. Morris, JC, Mohs, RC, Rogers, H, Fillenbaum, G, Heyman, A. Consortium to establish a registry for Alzheimer’s disease (CERAD) clinical and neuropathological assessment of Alzheimer’s disease. Psychopharm Bull 1988; 24: 641644.Google Scholar
19. Mirra, SS, Hart, MN, Terry, RD. Making the diagnosis of Alzheimer’s disease. Arch Pathol Lab Med 1993; 117: 132144.Google Scholar
20. Newell, KL, Hyman, BT, Growdon, JH, Hedley-Whyte, ET. Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer’s disease. J Neuropathol Exp Neurol 1999; 58: 11471155.CrossRefGoogle Scholar
21. Braak, H, Braak, E, Bohl, J. Staging of Alzheimer-related cortical destruction. Eur Neurol 1993; 33: 403408.Google Scholar
22. Averback, P. Two new lesions in Alzheimer’s disease. Lancet 1983;Google Scholar
23. Perl, DP, Good, PF. Uptake of aluminum into central nervous system along nasal-olfactory pathways. Lancet 1987; 1: 1028.Google Scholar
24. Ulrich, J. Alzheimer changes in nondemented patients younger than 65: possible early stages of Alzheimer’s disease and senile dementia of Alzheimer type. Ann Neurol 1985; 17: 273277.Google Scholar
25. Powell, TPS, Cowan, WM, Reisman, G. Olfactory relationships of the diencephalon. Nature 1963; 199: 710712.CrossRefGoogle ScholarPubMed
26. Roberts, E. Alzheimer’s disease may begin in the nose and may be caused by aluminosilicates. Neurobiol Aging 1986; 7: 561567.CrossRefGoogle ScholarPubMed