title: Increased CSF tau level is correlated with decreased lamina cribrosa thickness.
abstract: BACKGROUND
  This study was to investigate whether the previously proposed link between Alzheimer's disease (AD) and decreased retinal nerve fiber layer thickness could be explained by the relationship between abnormal CSF profiles and optic nerve head characteristics, focusing on the influence of CSF tau protein on the lamina cribrosa (LC) thickness (LCT).
  
  
  METHODS
  A total of 44 eyes from 18 patients with AD and 26 healthy subjects were subjected to enhanced-depth-imaging volume scanning of the optic nerve using spectral-domain optical coherence tomography. The B-scan images were constructed three-dimensionally using maximum intensity projection (MIP), and the LCT was measured at three locations (superior midperipheral, midhorizontal, and inferior midperipheral) using the thin-slab MIP images. CSF levels of amyloid β 1-42 peptide, (Aβ1-42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) were measured from CSF samples of each subject. The relationship between the level of CSF proteins and the LCT was determined using linear regression and fractional polynomial analyses.
  
  
  RESULTS
  Univariate regression analysis revealed that higher CSF levels of T-tau (P = 0.004) and P-tau181P (P = 0.027), as well as a smaller central corneal thickness (P = 0.032), were significantly associated with a smaller LCT. Multivariate analysis indicated that only CSF T-tau (P = 0.041) was significantly associated with the LCT. The relationship was well explained by both linear regression (R(2) = 0.179, P = 0.004) and fractional polynomial analysis (R(2) = 0.275, P = 0.001). When we performed an assessment by linear regression with an indicator, the relationship was significant both in the healthy and AD groups, with a stronger correlation found in the healthy group (regression coefficients = -1.098 vs. -0.280, P = 0.018).
  
  
  CONCLUSIONS
  An increased CSF level of T-tau was significantly associated with a thinner LCT in both the healthy and AD groups. This result suggests that LCT could serve as a potential non-invasive indicator for increased CSF tau. The clinical meaning of the higher level of CSF T-tau in axonal degeneration of the optic nerve remains to be determined.
authors: Department of Ophthalmology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. opticdisc@gmail.com.
authors: Eun Ji
authors: EJ
authors: Lee
authors: Department of Ophthalmology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. twkim7@snu.ac.kr.
authors: Tae-Woo
authors: TW
authors: Kim
authors: Department of Ophthalmology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. saladin85@hanmail.net.
authors: Dae Seung
authors: DS
authors: Lee
authors: Department of Applied Statistics, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, 120-749, Seoul, South Korea. hkim@yonsei.ac.kr.
authors: Hyunjoong
authors: H
authors: Kim
authors: Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. kumimesy@gmail.com.
authors: Young Ho
authors: YH
authors: Park
authors: Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. jekim220@gmail.com.
authors: Jungeun
authors: J
authors: Kim
authors: Department of Radiology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. joonwoo2@gmail.com.
authors: Joon Woo
authors: JW
authors: Lee
authors: Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro, 173 Beon-gil, Bundang-gu, 463-707, Seongnam, Gyeonggi-do, South Korea. neuroksy@snu.ac.kr.
authors: SangYun
authors: S
authors: Kim
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D009898:Optic Disk / Q000473:pathology*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D041623:Tomography, Optical Coherence; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins