title: Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients.
abstract: 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.
authors.affiliation: Tongji Medical College, HUST, Wuhan 430030, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Hu
authors.forename: Shan-Shu
authors.initials: SS
authors.lastname: He
authors.forename: Xiao-Chuang
authors.initials: XC
authors.lastname: Wang
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Duan
authors.forename: Sabiha
authors.initials: S
authors.lastname: Khatoon
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
mesh_terms: 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
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins; C051774:neurofilament protein H; C061195:neurofilament protein M