Revisiting the Cerebrospinal Fluid Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus: The Bologna Pro-Hydro Study

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Abstract

Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in idiopathic normal pressure hydrocephalus (iNPH) with the aim of a better differential diagnosis, but the pathophysiological mechanisms underlying CSF biomarker changes and the relationship between biomarker levels and clinical variables are still a matter of debate. We evaluated CSF amyloid-β (Aβ) 42 and Aβ 40, total (t)-tau, phosphorylated (p)-tau, total prion protein (t-PrP), and neurofilament light chain protein (NfL) in healthy controls (n=50) and subjects with iNPH (n=71), Alzheimer's disease (AD) (n=60), and several other subtypes of dementia (n=145). Patients with iNPH showed significantly lower levels of Aβ 42, Aβ 40, t-tau, and p-tau compared to controls. Similarly, t-PrP values showed a trend toward lower levels in iNPH patients than in controls. At variance, NfL levels were increased in iNPH as in all other neurodegenerative dementias, with no significant difference between "pure" iNPH cases and those with vascular or AD comorbidities. The Aβ 42 /Aβ 40 ratio showed higher diagnostic value than Aβ 42 alone in the differential diagnosis between iNPH and AD. There were no clinically relevant associations between neuroimaging markers, scores at clinical and cognitive scales/tests, or rates of response at tap test and CSF biomarker results. In summary, the CSF biomarker signature in patients with iNPH is mainly characterized by reduced CSF concentrations of Aβ- and tau-related proteins. The assessment of CSF neurodegenerative biomarker profile in iNPH, including the Aβ 42 /Aβ 40 ratio, contributes to the differential diagnosis with AD and other dementias but shows poor associations with clinical variables.

Original languageEnglish
Pages (from-to)723-733
Number of pages11
JournalJournal of Alzheimer's Disease
Volume68
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Normal Pressure Hydrocephalus
Cerebrospinal Fluid
Biomarkers
Alzheimer Disease
Dementia
Differential Diagnosis
tau Proteins
Vascular Diseases
Amyloid
Neuroimaging
Comorbidity

Keywords

  • Alzheimer's disease
  • amyloid
  • Aβ 42 /Aβ 40 ratio
  • dementia with Lewy bodies
  • frontotemporal dementia
  • neurofilament light chain protein
  • prion protein
  • tau
  • vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

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title = "Revisiting the Cerebrospinal Fluid Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus: The Bologna Pro-Hydro Study",
abstract = "Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in idiopathic normal pressure hydrocephalus (iNPH) with the aim of a better differential diagnosis, but the pathophysiological mechanisms underlying CSF biomarker changes and the relationship between biomarker levels and clinical variables are still a matter of debate. We evaluated CSF amyloid-β (Aβ) 42 and Aβ 40, total (t)-tau, phosphorylated (p)-tau, total prion protein (t-PrP), and neurofilament light chain protein (NfL) in healthy controls (n=50) and subjects with iNPH (n=71), Alzheimer's disease (AD) (n=60), and several other subtypes of dementia (n=145). Patients with iNPH showed significantly lower levels of Aβ 42, Aβ 40, t-tau, and p-tau compared to controls. Similarly, t-PrP values showed a trend toward lower levels in iNPH patients than in controls. At variance, NfL levels were increased in iNPH as in all other neurodegenerative dementias, with no significant difference between {"}pure{"} iNPH cases and those with vascular or AD comorbidities. The Aβ 42 /Aβ 40 ratio showed higher diagnostic value than Aβ 42 alone in the differential diagnosis between iNPH and AD. There were no clinically relevant associations between neuroimaging markers, scores at clinical and cognitive scales/tests, or rates of response at tap test and CSF biomarker results. In summary, the CSF biomarker signature in patients with iNPH is mainly characterized by reduced CSF concentrations of Aβ- and tau-related proteins. The assessment of CSF neurodegenerative biomarker profile in iNPH, including the Aβ 42 /Aβ 40 ratio, contributes to the differential diagnosis with AD and other dementias but shows poor associations with clinical variables.",
keywords = "Alzheimer's disease, amyloid, Aβ 42 /Aβ 40 ratio, dementia with Lewy bodies, frontotemporal dementia, neurofilament light chain protein, prion protein, tau, vascular dementia",
author = "Samir Abu-Rumeileh and Giulia Giannini and Barbara Polischi and Luca Albini-Riccioli and David Milletti and Federico Oppi and Michelangelo Stanzani-Maserati and Sabina Capellari and Paolo Mantovani and Giorgio Palandri and Pietro Cortelli and Sabina Cevoli and Piero Parchi",
note = "Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Universit{\`a} di Bologna (Capellari Sabina, Cortelli Pietro, Parchi Piero)",
year = "2019",
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doi = "10.3233/JAD-181012",
language = "English",
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TY - JOUR

T1 - Revisiting the Cerebrospinal Fluid Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus

T2 - The Bologna Pro-Hydro Study

AU - Abu-Rumeileh, Samir

AU - Giannini, Giulia

AU - Polischi, Barbara

AU - Albini-Riccioli, Luca

AU - Milletti, David

AU - Oppi, Federico

AU - Stanzani-Maserati, Michelangelo

AU - Capellari, Sabina

AU - Mantovani, Paolo

AU - Palandri, Giorgio

AU - Cortelli, Pietro

AU - Cevoli, Sabina

AU - Parchi, Piero

N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Capellari Sabina, Cortelli Pietro, Parchi Piero)

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in idiopathic normal pressure hydrocephalus (iNPH) with the aim of a better differential diagnosis, but the pathophysiological mechanisms underlying CSF biomarker changes and the relationship between biomarker levels and clinical variables are still a matter of debate. We evaluated CSF amyloid-β (Aβ) 42 and Aβ 40, total (t)-tau, phosphorylated (p)-tau, total prion protein (t-PrP), and neurofilament light chain protein (NfL) in healthy controls (n=50) and subjects with iNPH (n=71), Alzheimer's disease (AD) (n=60), and several other subtypes of dementia (n=145). Patients with iNPH showed significantly lower levels of Aβ 42, Aβ 40, t-tau, and p-tau compared to controls. Similarly, t-PrP values showed a trend toward lower levels in iNPH patients than in controls. At variance, NfL levels were increased in iNPH as in all other neurodegenerative dementias, with no significant difference between "pure" iNPH cases and those with vascular or AD comorbidities. The Aβ 42 /Aβ 40 ratio showed higher diagnostic value than Aβ 42 alone in the differential diagnosis between iNPH and AD. There were no clinically relevant associations between neuroimaging markers, scores at clinical and cognitive scales/tests, or rates of response at tap test and CSF biomarker results. In summary, the CSF biomarker signature in patients with iNPH is mainly characterized by reduced CSF concentrations of Aβ- and tau-related proteins. The assessment of CSF neurodegenerative biomarker profile in iNPH, including the Aβ 42 /Aβ 40 ratio, contributes to the differential diagnosis with AD and other dementias but shows poor associations with clinical variables.

AB - Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in idiopathic normal pressure hydrocephalus (iNPH) with the aim of a better differential diagnosis, but the pathophysiological mechanisms underlying CSF biomarker changes and the relationship between biomarker levels and clinical variables are still a matter of debate. We evaluated CSF amyloid-β (Aβ) 42 and Aβ 40, total (t)-tau, phosphorylated (p)-tau, total prion protein (t-PrP), and neurofilament light chain protein (NfL) in healthy controls (n=50) and subjects with iNPH (n=71), Alzheimer's disease (AD) (n=60), and several other subtypes of dementia (n=145). Patients with iNPH showed significantly lower levels of Aβ 42, Aβ 40, t-tau, and p-tau compared to controls. Similarly, t-PrP values showed a trend toward lower levels in iNPH patients than in controls. At variance, NfL levels were increased in iNPH as in all other neurodegenerative dementias, with no significant difference between "pure" iNPH cases and those with vascular or AD comorbidities. The Aβ 42 /Aβ 40 ratio showed higher diagnostic value than Aβ 42 alone in the differential diagnosis between iNPH and AD. There were no clinically relevant associations between neuroimaging markers, scores at clinical and cognitive scales/tests, or rates of response at tap test and CSF biomarker results. In summary, the CSF biomarker signature in patients with iNPH is mainly characterized by reduced CSF concentrations of Aβ- and tau-related proteins. The assessment of CSF neurodegenerative biomarker profile in iNPH, including the Aβ 42 /Aβ 40 ratio, contributes to the differential diagnosis with AD and other dementias but shows poor associations with clinical variables.

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KW - Aβ 42 /Aβ 40 ratio

KW - dementia with Lewy bodies

KW - frontotemporal dementia

KW - neurofilament light chain protein

KW - prion protein

KW - tau

KW - vascular dementia

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