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Idiopathic normal-pressure hydrocephalus: pathophysiology and diagnosis by CSF biomarkers
Anna Jeppsson1, Henrik Zetterberg, Kaj Blennow
1Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. gusjeppa@student.gu.se
Objectives:
This observational study aimed to explore the pathophysiology of idiopathic normal-pressure hydrocephalus (iNPH) and to evaluate the diagnostic and prognostic value of CSF biomarkers.
Methods:
Lumbar CSF of patients with iNPH and healthy elderly individuals (HI) and ventricular CSF (VCSF) from the patients with iNPH pre and 6 months postsurgery were analyzed by ELISA. We analyzed neurofilament light protein (NFL), myelin basic protein (MBP), a panel of β-amyloid isoforms (Aβ38, Aβ40, and Aβ42), soluble amyloid precursor protein (sAPP) isoforms sAPPα and sAPPβ, total and phosphorylated tau protein (t- and p-tau), and inflammatory markers interleukin 8, interleukin 10, and monocyte chemoattractant protein 1.
Results:
NFL was elevated and amyloid precursor protein (APP)-derived proteins and tau proteins were lower in patients with iNPH than in HI. Postsurgery, there was an increase of NFL, APP-derived proteins, p-tau, and albumin in VCSF, whereas levels of MBP and t-tau had decreased. Improved patients showed a greater increase of APP-derived proteins in VCSF following shunting than did those who did not improve.
Conclusions:
We interpret our data as iNPH pathophysiology to be characterized by a reduced periventricular metabolism and axonal degeneration but no major cortical damage.
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