Cell cycle kinesis in lymphocytes in the diagnosis of Alzheimer's disease.
The currently available clinical diagnostic tools do not allow an accurate and reliable diagnosis of Alzheimer's disease (AD) in other than demented patients. Furthermore, they do not allow the identification of subjects with pre-clinical AD. Cell cycle regulatory failure in neurones appears to be a very early event in the pathogenesis of AD. Our earlier findings indicate that there is a specific failure of the G1/S transition checkpoint that may not be restricted to neurones alone. We tested the possibility that lymphocytes of AD sufferers may also show signs of G1 regulatory failure. We found that the in vitro responsiveness of lymphocytes to G1 inhibitor treatment was significantly less effective in AD patients than in control subjects. Additionally, in subjects showing neuropsychological signs of pre-clinical AD, the lymphocyte response was similar to that seen in AD patients. We present direct evidence to support the hypothesis that the failure of the G1/S transition control is not restricted to neurones in AD patients, but occurs in peripheral cells, such as lymphocytes, as well. Our findings could provide the basis for new clinical tests that rely on eliciting the activation of the G1/S transition checkpoint in lymphocyte cultures. We propose that the introduction of the test could be useful in identifying people who do not yet fulfil the requirements of the NINCDS criteria for dementia, but who would benefit from the use of preventive measures for AD.
Nagy
Zsuzsanna
Z
OPTIMA, Department of Neuropathology, Radcliffe Infirmary NHS Trust, University of Oxford, Woodstock Road, Oxford OX2 6HE, UK. zsuzsa.nagy@pharm.ox.ac.uk
Combrinck
Marc
M
Budge
Marc
M
McShane
Rupert
R
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003704:Dementia / Q000175:diagnosis / Q000473:pathology; D003937:Diagnosis, Differential; D004317:Doxorubicin / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D009483:Neuropsychological Tests; D009928:Organ Specificity; D018384:Oxidative Stress; D010835:Phytohemagglutinins / Q000494:pharmacology; D018570:Risk Assessment; D020123:Sirolimus / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004317:Doxorubicin; D020123:Sirolimus