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.
Cogswell
John P
JP
Department of Pharmacogenetics, GlaxoSmithKline Inc., Research Triangle Park, NC 27709, USA. John.P.Cogswell@gsk.com
Ward
James
J
Taylor
Ian A
IA
Waters
Michelle
M
Shi
Yunling
Y
Cannon
Brian
B
Kelnar
Kevin
K
Kemppainen
Jon
J
Brown
David
D
Chen
Caifu
C
Prinjha
Rab K
RK
Richardson
Jill C
JC
Saunders
Ann M
AM
Roses
Allen D
AD
Richards
Cynthia A
CA
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