Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms

被引:122
作者
Hol, EM
Roelofs, RF
Moraal, E
Sonnemans, MAF
Sluijs, JA
Proper, EA
de Graan, PNE
Fischer, DF
van Leeuwen, FW
机构
[1] Netherlands Inst Brain Res, NL-1105 AZ Amsterdam, Netherlands
[2] UMCU, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands
关键词
glial fibrillary acidic protein; aberrant splicing; neurofibrillary tangles; Alzheimer's disease; Down syndrome; neurodegenerative disease; FIBRILLARY ACIDIC PROTEIN; AMYLOID PRECURSOR PROTEIN; NEUROFIBRILLARY TANGLES; FRAMESHIFT MUTATIONS; DISEASE PATHOLOGY; ALEXANDER-DISEASE; BRAIN; GENE; CELL; ASTROCYTES;
D O I
10.1038/sj.mp.4001379
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glial fibrillary acidic protein (GFAP) is considered to be a highly specific marker for glia. Here, we report on the expression of GFAP in neurons in the human hippocampus. Intriguingly, this neuronal GFAP is coded by out-of-frame splice variants and its expression is associated with Alzheimer pathology. We identified three novel GFAP splice forms: Delta 135 nt, Delta exon 6 and Delta 164 nt. Neuronal GFAP is mainly observed in the pyramidal neurons of the hippocampus of Alzheimer and Down syndrome patients and aged controls, but not in neurons of patients suffering from hippocampal sclerosis. Apparently, the hippocampal neurons in patients with Alzheimer's disease pathology are capable of expressing glia-specific genes.
引用
收藏
页码:786 / 796
页数:11
相关论文
共 47 条
[1]   Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules [J].
Alonso, AD ;
GrundkeIqbal, I ;
Iqbal, K .
NATURE MEDICINE, 1996, 2 (07) :783-787
[2]   A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease [J].
Aoki, Y ;
Haginoya, K ;
Munakata, M ;
Yokoyama, H ;
Nishio, T ;
Togashi, N ;
Ito, T ;
Suzuki, Y ;
Kure, S ;
Iinuma, K ;
Brenner, M ;
Matsubara, Y .
NEUROSCIENCE LETTERS, 2001, 312 (02) :71-74
[3]   PATTERNS OF GLIOSIS IN ALZHEIMERS-DISEASE AND AGING CEREBRUM [J].
BEACH, TG ;
WALKER, R ;
MCGEER, EG .
GLIA, 1989, 2 (06) :420-436
[4]   CENTRAL NERVOUS-SYSTEM PATHOLOGY OF TUBEROUS SCLEROSIS IN CHILDREN [J].
BENDER, BL ;
YUNIS, EJ .
ULTRASTRUCTURAL PATHOLOGY, 1980, 1 (03) :287-299
[5]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[6]   Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease [J].
Brenner, M ;
Johnson, AB ;
Boespflug-Tanguy, O ;
Rodriguez, D ;
Goldman, JE ;
Messing, A .
NATURE GENETICS, 2001, 27 (01) :117-120
[7]   STRUCTURE AND TRANSCRIPTIONAL REGULATION OF THE GFAP GENE [J].
BRENNER, M .
BRAIN PATHOLOGY, 1994, 4 (03) :245-257
[8]  
Condorelli DF, 1999, J NEUROSCI RES, V56, P219, DOI 10.1002/(SICI)1097-4547(19990501)56:3<219::AID-JNR1>3.0.CO
[9]  
2-2
[10]  
DAHL D, 1976, BRAIN RES, V116, P150, DOI 10.1016/0006-8993(76)90257-2