Cell cycle markers in the hippocampus in Alzheimer’s disease

Using immunohistochemistry we have analysed the nuclear expression of cyclins A, B, D, and E in neurones in the hippocampi of control subjects and patients suffering from various neurodegenerative disorders including Alzheimer’s disease (AD). Cyclins A and D could not be detected but varying degrees of cyclin E expression were found in all patient groups including control subjects. Cyclin B expression was not detected in control subjects but it was expressed in the subiculum, dentate gyrus and CA1 region in patients with AD-type pathology and in the CA2 region and the dentate gyrus of cases of Pick’s disease. These reults suggest that some neurones may have re-entered the cell cycle. The expression of cyclin E without cyclin A expression may indicate an arrest in G₁ with the possibility of re-differentiation and exit from G₁ to G₀. The expression pattern of cyclin E indicates that re-entry into the cell cycle is possible even in control patients, but it is accentuated in patients with AD-related pathology. However, cyclin B was only expressed in AD patients and occurred in areas that were severely affected by pathology. Neurones with cyclin B-reactive nuclei in AD were AT8 positive but did not contain fully developed tangles. In neurones, where cyclin B is expressed, it would appear that the G₁/S checkpoint has been bypassed and that the cell cycle is arrested in G₂. It is proposed that these neurones do not have the opportunity for subsequent re-differentiation. Since factors known to be present in G₂ seem to be responsible for microtubule destabilisation and hyperphosphorylation of tau we hypothesise that cell cycle disturbances may be important in the pathogenesis of AD. Received: 26 September 1996 / Revised, accepted: 20 November 1996