Multivariate analysis of differential lymphocyte cell cycle activity in Alzheimer's disease

• Published in: Neurobiology of aging Vol. 33; no. 2; pp. 234 - 241
• Main Authors: Stieler, Jens, Grimes, Randy, Weber, Don, Gartner, William, Sabbagh, Marwan, Arendt, Thomas
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.02.2012; Elsevier
• Subjects: Aged; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer Disease - immunology; Biological and medical sciences; Biomarker; Cell Cycle - immunology; Cell cycle activation; Cell Cycle Proteins - immunology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Development. Senescence. Regeneration. Transplantation; Diagnosis; Female; Fundamental and applied biological sciences. Psychology; Humans; Internal Medicine; Lymphocyte Activation - immunology; Lymphocytes - immunology; Lymphocytes - pathology; Male; Medical sciences; Multivariate Analysis; Neurology; Parkinson's disease dementia; Peripheral blood lymphocytes; Reproducibility of Results; Sensitivity and Specificity; Vertebrates: nervous system and sense organs; Biomarker; Diagnosis; Peripheral blood lymphocytes; Cell cycle activation; Parkinson's disease dementia; Dementia; Nervous system diseases; Senescence; Alzheimer disease; Parkinson disease; Biological marker; Cerebral disorder; Central nervous system disease; Cell cycle; Degenerative disease; Lymphocyte; Extrapyramidal syndrome
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2010.03.001

Mounting evidence suggests cell cycle dysregulation is involved in the pathogenesis of Alzheimer's disease (AD) and that this failure is systemic, affecting not only neurons but also peripheral blood lymphocytes (PBLs). This study analyzed if differences in PBL proliferation activity could be used as a diagnostic biomarker for AD. CD69 and CD28 expressions on PBL T, B, and monocyte cells were measured by flow cytometry with and without mitogenic stimulation in healthy controls (HC), probable AD, and Parkinson's disease dementia (PDD) subjects. Univariate and multivariate scoring models were employed to evaluate the data relative to the clinical diagnoses. Eleven CD expression markers were significantly altered in AD subjects compared with a mixed pool of PDD and HC subjects using univariate models. Using multivariate models, seven CD expression markers were significantly altered in AD subjects compared with PDD subjects. Multivariate scoring demonstrated up to a 91% positive and 92% negative agreement with subject clinical diagnosis and had little correlation with the severity of dementia. Present findings suggest that with further development this analytical and multivariate modeling procedure could aid the current differential diagnosis of Alzheimer's disease.