Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients.
Neurofilament (NF) subunits NF-H, NF-M and NF-L are hyperphosphorylated and elevated in Alzheimer disease (AD) brain. We investigated the level and phosphorylation states of NF subunits in lumbar cerebrospinal fluid (CSF) from living patients by bienzyme substrate-recycle enzyme-linked immunosorbent assay. We found: (i), that the levels of phosphorylated NF-H/M (pNF-H/M), non-phosphorylated NF-H/M (npNF-H/M) and NF-L were significantly higher (pNF-H/M, approximately 12-24-fold; npNF-H/M, approximately 3-4-fold) in neurologically healthy aged people than young control individuals; (ii), that in AD, the levels of npNF-H/M, and NF-L were similar to vascular dementia (VaD), and higher than in age-matched controls; and (iii), that the levels of pNF-H/M were significantly higher than in aged controls, non-AD neurological disorders and VaD. Based on these findings, it is suggested that the increased level of total NF proteins in CSF could be used as a marker for brain aging and neurodegenerative disorders in general, and the levels of pNF-H/M as a marker to discriminate AD from normal brain aging and as well as neurological conditions including VaD.
Hu
Yuan-Yuan
YY
Tongji Medical College, HUST, Wuhan 430030, PR China.
He
Shan-Shu
SS
Wang
Xiao-Chuang
XC
Duan
Qiu-Hong
QH
Khatoon
Sabiha
S
Iqbal
Khalid
K
Grundke-Iqbal
Inge
I
Wang
Jian-Zhi
JZ
D000293:Adolescent; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D015854:Up-Regulation / Q000502:physiology*; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins; C051774:neurofilament protein H; C061195:neurofilament protein M