Rapid increase of ‘brain-type’ transferrin in cerebrospinal fluid after shunt surgery for idiopathic normal pressure hydrocephalus: a prognosis marker for cognitive recovery

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity. The prognosis for cognitive improvement after shunt surgery has been difficult to predict. We therefore investigated various CSF proteins, hoping to find a biomarker predictive of cognitive performance one to two years after shunt surgery. CSF proteins of 34 iNPH and 15 non-iNPH patients were analysed by Western blotting, revealing two glycan isoforms of transferrin (Tf); 'brain-type' Tf with N-acetylglucosaminylated glycans and 'serum-type' Tf with α2, 6-sialylated glycans. Brain-type Tf levels decreased in iNPH but rapidly returned to normal levels within 1-3 months after shunt surgery. This change was positively correlated with recovery from dementia, per Mini-Mental State Examination and Frontal Assessment Battery scores at 11.8 ± 7.7 months post-operation, suggesting that brain-type Tf is a prognostic marker for recovery from dementia after shunt surgery for iNPH. Histochemical staining with anti-Tf antibody and an N-acetylglucosamine-binding lectin suggests that brain-type Tf is secreted from choroid plexus, CSF-producing tissue.

Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus

“…Другие биомаркеры. Существуют и прочие биомаркеры, которые использовались для диагностики иНТГ: основной белок миелина (myelin basic protein, MBP); трансформирующий ростовой фактор β (тransforming growth factor beta, TGFβ); интерлейкины 1, 6, 10; фактор некроза опухолей α (tumor necrosis factor alfa, TNFα); трансферрин, однако результаты проведенных исследований являются сомнительными, убедительных доказательств в пользу целесообразности их обязательного использования при диагностике синдрома Хакима-Адамса нет [9,16,23,25,41,42].…”

Myotonic dystrophy type 1 accompanied with normal pressure hydrocephalus: a case report and literature review

“…The mechanism of NPH may be the obliteration of arachnoid villi (small protrusions of the arachnoid mater which can return CSF to the venous circulation), leading to the disturbances of CSF reabsorption, leading to disrupted CSF reabsorption and subsequent ventricular enlargement [48,49]. The possible mechanism of NPH in DM1 patients may be related to widespread cell membrane defects caused by genetic abnormalities [14], leading to the arachnoid granulations [48,50,51]. However, the association between DM1 and NPH can be overlooked for several reasons.…”

Transferrin isoforms in cerebrospinal fluid and their relation to neurological diseases

“…These results suggest that the epithelium specifically expresses GlcNAc-terminated glycoproteins in choroid plexus tissue and possibly produces brain-type Tf. 23)…”