A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative dementia. Approximately 10% of cases present at an age of onset before 65 years old, which in turn can be monogenic familial AD (FAD) or sporadic early-onset AD (sEOAD). Mutations in PSEN1, PSEN2, and APP genes have been linked with FAD. The aim of our study is to describe the brain whole-genome RNA expression profile of the posterior cingulate area in sEOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). Fourteen patients (7 sEOAD and 7 FAD-PSEN1) and 7 neurologically healthy control subjects were selected and whole-genome expression was measured using Affymetrix Human Gene 1.1 microarrays. We identified statistically significant expression changes in sEOAD and FAD-PSEN1 brains with respect to control subjects (3183 and 3350 differentially expressed genes [DEG] respectively, false discovery rate-corrected p < 0.05). Of them, 1916 DEG were common between the 2 comparisons. We did not identify DEG between sEOAD and FAD-PSEN1. Microarray data were validated through real-time quantitative polymerase chain reaction. In silico analysis of DEG revealed an alteration in biological pathways related to intracellular signaling pathways (particularly calcium signaling), neuroactive ligand-receptor interactions, axon guidance, and long-term potentiation in both groups of patients. In conclusion, the altered biological final pathways in sEOAD and FAD-PSEN1 are mainly related with cell signaling cascades, synaptic plasticity, and learning and memory processes. We hypothesize that these 2 groups of early-onset AD with distinct etiologies and likely different could present a neurodegenerative process with potential different pathways that might converge in a common and similar final stage of the disease.
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain. antonell@clinic.ub.es.
Anna
A
Antonell
Albert
A
Lladó
Jordi
J
Altirriba
Teresa
T
Botta-Orfila
Mircea
M
Balasa
Manel
M
Fernández
Isidre
I
Ferrer
Raquel
R
Sánchez-Valle
José Luis
JL
Molinuevo
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human / Q000235:genetics*; D006179:Gyrus Cinguli / Q000473:pathology / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics
C508853:PSEN1 protein, human; D053764:Presenilin-1