Altered Blood Gene Expression of Tumor-Related Genes (PRKCB, BECN1, and CDKN2A) in Alzheimer's Disease.
Alzheimer's disease (AD) is the most common of the neurodegenerative diseases. Recent diagnostic criteria have defined a preclinical disease phase during which neuropathological substrates are thought to be present in the brain. There is an urgent need to find measurable alterations in this phase as well as a good peripheral biomarker in the blood. We selected a cohort of 100 subjects (controls = 47; preclinical AD = 11; patients with AD = 42) and analyzed whole blood expression of 20 genes by quantitative polymerase chain reaction. The selected genes belonged to calcium signaling, senescence and autophagy, and mitochondria/oxidative stress pathways. Additionally, two genes associated with an increased risk of developing AD (clusterin (CLU) and bridging integrator 1 (BIN1)) were also analyzed. We detected significantly different gene expressions of BECN1 and PRKCB between the control and the AD groups and of CDKN2A between the control and the preclinical AD groups. Notably, these three genes are also considered tumor suppressor (CDKN2A and BECN1) or tumor promoter (PRKCB) genes. Gene-gene expression Pearson correlations were computed separately for controls and patients with AD. The significant correlations (p < 0.001) were represented in a network analysis with Cytoscape tool, which suggested an uncoupling of mitochondria-related genes in AD group. Whole blood is emerging as a valuable tissue in the study of the physiopathology of AD.
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. antonell@clinic.ub.es.
Anna
A
Antonell
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Albert
A
Lladó
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Raquel
R
Sánchez-Valle
Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB)-Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
Coral
C
Sanfeliu
Bioinformatics Core Facility, IDIBAPS-CEK, Hospital Clínic/Universitat de Barcelona, Barcelona, Spain.
Teresa
T
Casserras
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Lorena
L
Rami
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Cristina
C
Muñoz-García
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Adrià
A
Dangla-Valls
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Mircea
M
Balasa
Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Patricia
P
Boya
Bioinformatics Core Facility, IDIBAPS-CEK, Hospital Clínic/Universitat de Barcelona, Barcelona, Spain.
Susana G
SG
Kalko
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
José Luis
JL
Molinuevo
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D000071186:Beclin-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D064546:Protein Kinase C beta / Q000097:blood / Q000235:genetics* / Q000378:metabolism
C491997:BECN1 protein, human; D000071186:Beclin-1; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C579054:PRKCB protein, human; D064546:Protein Kinase C beta
Alzheimer’s disease; Autophagy; Blood; Gene expression; Mitochondria; Preclinical