Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways.
MicroRNAs have essential functional roles in brain development and neuronal specification but their roles in neurodegenerative diseases such as Alzheimer's disease (AD) is unknown. Using a sensitive qRT-PCR platform we identified regional and stage-specific deregulation of miRNA expression in AD patient brains. We used experimental validation in addition to literature to reveal how the deregulated brain microRNAs are biomarkers for known and novel pathways in AD pathogenesis related to amyloid processing, neurogenesis, insulin resistance, and innate immunity. We additionally recovered miRNAs from cerebrospinal fluid and discovered AD-specific miRNA changes consistent with their role as potential biomarkers of disease.
Department of Pharmacogenetics, GlaxoSmithKline Inc., Research Triangle Park, NC 27709, USA. John.P.Cogswell@gsk.com
John P
JP
Cogswell
James
J
Ward
Ian A
IA
Taylor
Michelle
M
Waters
Yunling
Y
Shi
Brian
B
Cannon
Kevin
K
Kelnar
Jon
J
Kemppainen
David
D
Brown
Caifu
C
Chen
Rab K
RK
Prinjha
Jill C
JC
Richardson
Ann M
AM
Saunders
Allen D
AD
Roses
Cynthia A
CA
Richards
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000134:cerebrospinal fluid* / Q000235:genetics*; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000682:Amyloid; D015415:Biomarkers; D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger