PMID- 37880775
OWN - NLM
STAT- MEDLINE
DCOM- 20231027
LR  - 20240210
IS  - 2045-8118 (Electronic)
IS  - 2045-8118 (Linking)
VI  - 20
IP  - 1
DP  - 2023 Oct 25
TI  - Association between ventricular CSF biomarkers and outcome after shunt surgery in 
      idiopathic normal pressure hydrocephalus.
PG  - 77
LID - 10.1186/s12987-023-00475-8 [doi]
LID - 77
AB  - INTRODUCTION: The relationship between neurochemical changes and outcome after 
      shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable 
      dementia and gait disorder, is unclear. We used baseline ventricular CSF to 
      explore associations to outcome, after shunting, of biomarkers selected to 
      reflect a range of pathophysiological processes. METHODS: In 119 consecutive 
      patients with iNPH, the iNPH scale was used before and after shunt surgery to 
      quantify outcome. Ventricular CSF was collected perioperatively and analyzed for 
      biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic 
      dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 
      (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light 
      (NfL), amyloid beta 38 (Abeta38), Abeta40, Abeta42, amyloid beta 42/40 ratio (Abeta42/40), 
      soluble amyloid precursor protein alfa (sAPPalpha), sAPPbeta, total tau (T-tau), 
      phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and 
      neurogranin. RESULTS: The neurogranin concentration was higher in improved (68%) 
      compared to unimproved patients (median 365 ng/L (IQR 186-544) vs 330 (205-456); 
      p = 0.046). A linear regression model controlled for age, sex and vascular risk 
      factors including neurogranin, T-tau, and GFAP, resulted in adjusted R(2) = 0.06, 
      p = 0.047. The Abeta42/40 ratio was bimodally distributed across all samples, as 
      well as in the subgroups of improved and unimproved patients but did not 
      contribute to outcome prediction. The preoperative MMSE score was lower within 
      the low Abeta ratio group (median 25, IQR 23-28) compared to the high subgroup (26, 
      24-29) (p = 0.028). The T-Tau x Abeta40/42 ratio and P-tau x Abeta40/42 ratio did not 
      contribute to shunt response prediction. The prevalence of vascular risk factors 
      did not affect shunt response. DISCUSSION: A higher preoperative ventricular CSF 
      level of neurogranin, which is a postsynaptic marker, may signal a favorable 
      postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers 
      explained only 6% of the variability in outcome. Evidence of amyloid or tau 
      pathology did not affect the outcome.
CI  - (c) 2023. BioMed Central Ltd., part of Springer Nature.
FAU - Gronning, Rebecca
AU  - Gronning R
AD  - Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of 
      Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Bla 
      Straket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden. 
      rebecca.gronning@neuro.gu.se.
FAU - Jeppsson, Anna
AU  - Jeppsson A
AD  - Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of 
      Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Bla 
      Straket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden.
FAU - Hellstrom, Per
AU  - Hellstrom P
AD  - Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of 
      Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Bla 
      Straket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden.
FAU - Laurell, Katarina
AU  - Laurell K
AD  - Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden.
FAU - Farahmand, Dan
AU  - Farahmand D
AD  - Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of 
      Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Bla 
      Straket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden.
FAU - Zetterberg, Henrik
AU  - Zetterberg H
AD  - Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, 
      Sweden.
AD  - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and 
      Physiology, Sahlgrenska Academy, University of Gothenburg, Molndal, Sweden.
AD  - Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen 
      Square, London, UK.
AD  - UK Dementia Research Institute at UCL, London, UK.
AD  - Institute at UCL, London, UK.
AD  - Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, 
      China.
AD  - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
FAU - Blennow, Kaj
AU  - Blennow K
AD  - Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, 
      Sweden.
AD  - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and 
      Physiology, Sahlgrenska Academy, University of Gothenburg, Molndal, Sweden.
FAU - Wikkelso, Carsten
AU  - Wikkelso C
AD  - Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of 
      Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Bla 
      Straket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden.
FAU - Tullberg, Mats
AU  - Tullberg M
AD  - Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of 
      Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Bla 
      Straket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden.
LA  - eng
GR  - R01 AG068398/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20231025
PL  - England
TA  - Fluids Barriers CNS
JT  - Fluids and barriers of the CNS
JID - 101553157
RN  - 0 (Amyloid beta-Peptides)
RN  - 132654-77-4 (Neurogranin)
RN  - 0 (tau Proteins)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - Amyloid beta-Peptides/metabolism
MH  - *Hydrocephalus, Normal Pressure/surgery/pathology
MH  - Neurogranin
MH  - tau Proteins/metabolism
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Biomarkers
MH  - *Alzheimer Disease
PMC - PMC10601279
OTO - NOTNLM
OT  - Amyloid
OT  - Cerebrospinal fluid
OT  - Neurodegeneration
OT  - Normal pressure hydrocephalus
OT  - Peritoneal catheter
OT  - Prediction
OT  - Ventricular catheter
COIS- HZ has served on scientific advisory boards and/or as a consultant for Abbvie, 
      Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, 
      AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon 
      Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens 
      Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia 
      sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a 
      co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part 
      of the Gothenburg University Ventures Incubator Program. The other authors 
      declare no competing interests.
EDAT- 2023/10/26 06:42
MHDA- 2023/10/27 06:43
PMCR- 2023/10/25
CRDT- 2023/10/26 00:06
PHST- 2023/04/19 00:00 [received]
PHST- 2023/10/06 00:00 [accepted]
PHST- 2023/10/27 06:43 [medline]
PHST- 2023/10/26 06:42 [pubmed]
PHST- 2023/10/26 00:06 [entrez]
PHST- 2023/10/25 00:00 [pmc-release]
AID - 10.1186/s12987-023-00475-8 [pii]
AID - 475 [pii]
AID - 10.1186/s12987-023-00475-8 [doi]
PST - epublish
SO  - Fluids Barriers CNS. 2023 Oct 25;20(1):77. doi: 10.1186/s12987-023-00475-8.