Isolation of neural precursor cells from Alzheimer's disease and aged control postmortem brain.
Recent studies demonstrate that isolated neural precursor cells are capable of generating neurons, astrocytes, and oligodendrocytes from neurogenic regions of adult brain. Because these studies use surgically resected or fresh postmortem specimens from young subjects, it is not clear whether neural precursor cells remain in the brain of normal aged subjects or subjects with Alzheimer's disease (AD). The purpose of this study was to determine if viable precursor cells remain in aged control and AD brain. AD subjects have significantly fewer viable precursor cells in the hippocampus compared with age-matched normal control subjects. Musashi-1 and Ki-67-positive precursor cells from AD self renew, but reach senescence earlier than cells isolated from normal aged control subjects. Precursor cells from AD and aged normal control specimens can differentiate into tubulin- and Tuj-1-positive neurons and GFAP-positive astrocytes. This study demonstrates that viable precursor cells remain in AD and aged normal control brain specimens and can be induced to differentiate. These results raise the possibility of stimulation of inherent precursor cells of aged individuals or AD patients to replace neurons lost in aging and/or neurodegeneration.
Sanders-Brown Center on Aging and Alzheimer's Disease Research Center, 800 S. Limestone St., 101 Sanders-Brown Bldg., University of Kentucky, Lexington, KY 40536-0230, USA. malove2@pop.uky.edu
Mark A
MA
Lovell
Hartmut
H
Geiger
Gary E
GE
Van Zant
Bert C
BC
Lynn
William R
WR
Markesbery
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D003933:Diagnosis; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D014404:Tubulin; C462941:beta3 tubulin, mouse