Dégénérescence corticobasale

English version: Corticobasal degeneration

Aspects cliniques:

Il s'agit d'une maladie neurodégénérative relativement rare qui touche essentiellement les régions cérébrales sous-corticales, puis corticales.

Les éléments les plus caractéristiques sont un dysfonctionnement moteur asymétrique (apraxie de la main gauche), une perte sensorielle corticale, et une apraxie sans détérioration intellectuelle à ce stade.

Mais le tableau clinique est souvent voisin de la Paralysie supranucléaire Progressive (PSP ou Maladie de Steele-Richardson-Olszewski): résistance à la L-dopa, tremblement d'attitude, syndrome pseudo-bulbaire avec dysarthrie, dysphagie, troubles oculomoteurs ainsi qu'une démence peuvent être associées.
 

La détérioration intellectuelle est associée à l'installation du processus dégénératif dans le cortex associatif (essentiellement le cortex frontal).

Neuropathologie:
 

• On peut observer une dégénérescence neurofibrillaire dans les noyaux sous corticaux ainsi que dans le cortex, et préférentiellement dans les régions frontales. Il y a également une perte neuronale et une gliose. Il y a également des cellules chromatolytiques (ou cellules de Pick, à ne pas confondre avec les corps de Pick). Les régions les plus touchées sont frontales et pariétales.
• La DNF affecte également les astrocytes pour former les "glial tangles" et les plaques astrocytaires. La technique de Gallyas (imprégnation argentique optimale pour la DNF) revèle des plaques astrocytaires en étoile pour la PSP (tufted plaques), alors que pour la CBD, le marquage est plutôt en couronne (astroyctic plaques).

Aspects moléculaires:

Le processus dégénératif est similaire à ce qui est observé dans la Paralysie Supranucléaire Progressive. Il s'agit d'une dégénérescence neurofibrillaire, avec accumulation de protéines tau (tauopathie). Le profil biochimique est un doublet de protéines tau (tau 64 et 69), comme dans la PSP.

Littérature:

Hyperphosphorylated tau proteins differentiate corticobasal degeneration and Pick's disease.

Buee Scherrer V, Hof PR, Buee L, Leveugle B, Vermersch P, Perl DP, Olanow CW, Delacourte A

Acta Neuropathol (Berl) 1996;91(4):351-359

In neurodegenerative disorders, hyperphosphorylated tau proteins aggregate into abnormal filaments. In the present study, tau protein alterations were studied in one corticobasal degeneration and seven Pick's disease cases using specific immunological probes. The typical lesions of corticobasal degeneration and Pick's disease were revealed by immunohistochemistry, including the presence of Pick bodies and achromatic swollen neurons, neuritic alterations, and neurofibrillary tangles. Tau-immunoreactive glial tangles were also observed. By immunoblotting, the case of corticobasal degeneration was characterized by the tau profile previously reported to occur in progressive supranuclear palsy with an intense labeling of the two tau 64 and 69 bands, while tau 55 was not visualized. In Pick's disease cases with Pick bodies and neurofibrillary tangles, a tau triplet similar to that encountered in Alzheimer's disease (tau 55, 64 and 69) was detected. Furthermore, a particular tau profile was found in four Pick's disease cases showing only Pick bodies and no neurofibrillary tangles. In these cases, tau 55 and 64 were strongly immunoreactive, whereas tau 69 was almost unlabeled. These differences are likely to be related to particular pools of tau isoforms present within the degenerating neurons. Since there is a great diversity of neurodegenerative disorders with substantial clinical and neuropathological overlap, the electrophoretic profile of tau proteins could represent a useful marker for the type of neurodegeneration.

PMID: 8928611, UI: 96254284

J Neurochem 1999 Mar;72(3):1243-9

Neurofibrillary degeneration in progressive supranuclear palsy and corticobasal degeneration: tau pathologies with exclusively "exon 10" isoforms.

Sergeant N, Wattez A, Delacourte A

INSERM Unite 422, Lille, France.

Pathological tau proteins that constitute the basic matrix of neuronal inclusions observed in numerous neurodegenerative disorders are disease specific. This is mainly the consequence of the aggregation of specific sets of tau isoforms according to the diseases, i.e., six isoforms in Alzheimer's disease (AD) and exclusively the three tau isoforms lacking the corresponding sequence of exon 10 (E10-) in Pick's disease (PiD). By using antibodies specific to the different tau isoforms and one- and two-dimensional gel electrophoresis followed by western blots, we demonstrate herein a third group of neurodegenerative disorders characterized by intraneuronal inclusions exclusively constituted of tau isoforms containing the sequence corresponding to exon 10, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Together, tau isoforms with exon 10 clearly differentiate three groups of neurodegenerative diseases: AD, PiD, and PSP/CBD. For each group, the neuropathological and clinical phenotypes are most likely related to specific sets of tau isoforms expressed by the vulnerable neuronal populations. The recently described mutations of the tau gene responsible for familial frontotemporal dementias also support this hypothesis.