Isolation of neural precursor cells from Alzheimer's disease and aged control postmortem brain

被引:44
作者
Lovell, Mark A.
Geiger, Hartmut
Van Zant, Gary E.
Lynn, Bert C.
Markesbery, William R.
机构
[1] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA
[2] Univ Kentucky, Alzheimers Dis Res Ctr, Lexington, KY 40536 USA
[3] Univ Kentucky, Dept Chem, Lexington, KY 40506 USA
[4] Univ Kentucky, Dept Internal Med, Lexington, KY 40536 USA
[5] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA
[6] Univ Kentucky, Dept Pathol, Lexington, KY 40536 USA
关键词
Alzheimer's disease; neural stem/precursor cells; neurodegeneration;
D O I
10.1016/j.neurobiolaging.2005.05.004
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Recent studies demonstrate that isolated neural precursor cells are capable of generating neurons, astrocytes, and oligodendrocytes front 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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:909 / 917
页数:9
相关论文
共 55 条
[1]  
AHMED S, 1995, J NEUROSCI, V15, P5765
[2]  
Arsenijevic Y, 1998, J NEUROSCI, V18, P2118
[3]  
Baird Andrew, 1994, Current Opinion in Neurobiology, V4, P78, DOI 10.1016/0959-4388(94)90035-3
[4]   Consensus recommendations for the postmortem diagnosis of Alzheimer's disease [J].
Ball, M ;
Braak, H ;
Coleman, P ;
Dickson, D ;
Duyckaerts, C ;
Gambetti, P ;
Hansen, L ;
Hyman, B ;
Jellinger, K ;
Markesbery, W ;
Perl, D ;
Powers, J ;
Price, J ;
Trojanowski, JQ ;
Wisniewski, H ;
Phelps, C ;
Khachaturian, Z .
NEUROBIOLOGY OF AGING, 1997, 18 (04) :S1-S2
[5]   In vitro expansion of a multipotent population of human neural progenitor cells [J].
Carpenter, MK ;
Cui, X ;
Hu, ZY ;
Jackson, J ;
Sherman, S ;
Seiger, Å ;
Wahlberg, LU .
EXPERIMENTAL NEUROLOGY, 1999, 158 (02) :265-278
[6]  
Chiasson BJ, 1999, J NEUROSCI, V19, P4462
[7]   A SELF-RENEWING MULTIPOTENTIAL STEM-CELL IN EMBRYONIC RAT CEREBRAL-CORTEX [J].
DAVIS, AA ;
TEMPLE, S .
NATURE, 1994, 372 (6503) :263-266
[8]   Subventricular zone astrocytes are neural stem cells in the adult mammalian brain [J].
Doetsch, F ;
Caillé, I ;
Lim, DA ;
García-Verdugo, JM ;
Alvarez-Buylla, A .
CELL, 1999, 97 (06) :703-716
[9]   Neurogenesis in the adult human hippocampus [J].
Eriksson, PS ;
Perfilieva, E ;
Björk-Eriksson, T ;
Alborn, AM ;
Nordborg, C ;
Peterson, DA ;
Gage, FH .
NATURE MEDICINE, 1998, 4 (11) :1313-1317
[10]   Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes [J].
Flax, JD ;
Aurora, S ;
Yang, CH ;
Simonin, C ;
Wills, AM ;
Billinghurst, LL ;
Jendoubi, M ;
Sidman, RL ;
Wolfe, JH ;
Kim, SU ;
Snyder, EY .
NATURE BIOTECHNOLOGY, 1998, 16 (11) :1033-1039