Preserved neurogenesis in non-demented individuals with AD neuropathology.
Rare individuals remain cognitively intact despite the presence of neuropathology usually associated with fully symptomatic Alzheimer's disease (AD), which we refer to as Non-Demented with Alzheimer's disease Neuropathology (NDAN). Understanding the involved mechanism(s) of their cognitive resistance may reveal novel strategies to treat AD-related dementia. In the pursuit of this goal, we determined the number of hippocampal neural stem cells (NSCs) and investigated the expression of several miRNAs in NDAN and AD subjects. Laser-capture microdissection of autopsy human hippocampus DG and qRT-PCR miRNA analyses were combined with immunofluorescence in this study. The number of SOX2(+) NSCs in the DG was significantly increased in NDAN individuals as compared to AD subjects. Further, the prevalence of SOX2(+) NSCs was found to correlate with cognitive capacity. Neurogenesis-regulating miRNAs were decreased in NDAN individuals as compared to AD patients. An increased number of NSCs and new neurons in NDAN individuals is associated with a unique expression of regulating miRNAs and strongly support a role of neurogenesis in mediating, in part, the ability of these individuals to resist the pathological burden of AD.
Mitchell Center for Neurodegenerative diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
David
D
Briley
Mitchell Center for Neurodegenerative diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
Valeria
V
Ghirardi
Department of Pathology, Oregon Health &Science University, OR, USA.
Randy
R
Woltjer
Mitchell Center for Neurodegenerative diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
Alicia
A
Renck
Mitchell Center for Neurodegenerative diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
Olga
O
Zolochevska
Mitchell Center for Neurodegenerative diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
Giulio
G
Taglialatela
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Maria-Adelaide
MA
Micci
D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D001344:Autopsy; D003704:Dementia / Q000150:complications / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D061346:Laser Capture Microdissection; D035683:MicroRNAs / Q000235:genetics; D058953:Neural Stem Cells / Q000473:pathology*; D055495:Neurogenesis / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000378:metabolism
D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors