Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease

• Background: Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail. Objective: To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer's disease (AD) biomarkers, amyloid-beta 42 (A beta(42)), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes. Methods: Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays. Results: Lower levels of NFL, NG, A beta(42), and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and A beta(42) were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with A beta(42), t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined. Conclusion: An addition of NFL to the CSF panel of A beta(42), t-tau, and p-tau may improve the differentiation of iNPH from SIVD.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Biomarkers

cerebrospinal fluid

normal pressure hydrocephalus

vascular

dementia

neurofilament light-chain

white-matter changes

alzheimers-disease

csf

biomarkers

total-tau

phosphorylated-tau

neurogranin

severity

degeneration

sclerosis

Neurosciences & Neurology

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