Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus

• Background: Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-beta (A beta) and alpha- and beta-cleaved soluble forms of amyloid precursor protein (sAPP alpha and sAPP beta). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery. Methods: Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), A beta isoforms A beta 38, A beta 40 and A beta 42, sAPP alpha, sAPP beta, APLP1 beta-derived peptides APL1 beta 25, APL1 beta 27 and APL1 beta 28 and YKL40 by immunochemical methods. Results: The concentrations of all soluble forms of APP, all A beta isoforms and APL1 beta 28 were lower, whilst APL1 beta 25 and APL1 beta 27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged. Conclusions: The reduced CSF concentrations of A beta 38, A beta 40, A beta 42, sAPPa and sAPP beta suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1 beta 25 and APL1 beta 27 in combination with a slight decreased APL1 beta 28 could be caused by more available gamma-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Neurodegeneration

Normal pressure hydrocephalus

Cerebrospinal fluid

Amyloid

NFL

YKL40

white-matter changes

cerebrospinal-fluid

precursor protein

csf

biomarkers

alzheimers-disease

beta-like

brain

tau

clearance

peptide

Neurosciences & Neurology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)