Biochemical studies in Normal Pressure Hydrocephalus (NPH) patients: Change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Aβ) peptide and phospho-tau

Balmiki Ray, Patricio F. Reyes, Debomoy Lahiri

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29 Citations (Scopus)

Abstract

Normal Pressure Hydrocephalus (NPH) is one of the causes of dementia of the elderly characterized by impaired mental function, gait difficulties and urinary incontinence. Previously, it was proposed that some of the NPH patients may develop Alzheimer's disease (AD) like pathology. Aim of this study was to compare levels of different CSF biomarkers, including total secreted β-amyloid precursor protein (sAPP), sAPP-alpha form (sAPPα), amyloid-beta (Aβ) peptide, total-tau protein and hyperphosphorylated-tau protein in subjects from NPH and Non-NPH Control (NNC). CSF was collected from 23 NPH patients and 13 Non-NPH controls by lumber puncture. Western blot analysis was performed to measure levels of sAPP-total. ELISA was used separately to determine levels of sAPPα, Aβ peptide, total-tau and phospho-tau proteins. We found a significant decrease in levels of total secreted APP, sAPPα and Aβ (1-42) in the CSF sample of NPH patients vs. NNC. We did not observe any change in levels of total-tau or phospho-tau in NPH vs. NNC subjects. Notably, phospho-tau level was significantly increased in the NPH patients, who were suffering from the disease for more than one year, vs. NNC. Among five biomarkers studied, decreased sAPP, sAPPα and Aβ (1-42) levels in CSF can be molecular markers to distinguish NPH cases from NNC. Disease severity can also be assessed by increased levels of CSF phospho-tau protein and the ratio of phospho-tau to Aβ (1-42), which might be a useful tool for predicting conversion of NPH individuals to other neurodegenerative disorders including Alzheimer's disease (AD).

Original languageEnglish
Pages (from-to)539-547
Number of pages9
JournalJournal of Psychiatric Research
Volume45
Issue number4
DOIs
StatePublished - Apr 2011

Fingerprint

Normal Pressure Hydrocephalus
Amyloid beta-Protein Precursor
Amyloid beta-Peptides
Serum Amyloid A Protein
tau Proteins
Hydrocephalus
Alzheimer Disease
Biomarkers
Pressure
Urinary Incontinence
Gait
Punctures
Neurodegenerative Diseases
Dementia
Western Blotting
Enzyme-Linked Immunosorbent Assay
Pathology

Keywords

  • Amyloid beta-peptide
  • Cerebrospinal fluid
  • Clearance
  • Disease progression
  • NPH
  • Tau

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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title = "Biochemical studies in Normal Pressure Hydrocephalus (NPH) patients: Change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Aβ) peptide and phospho-tau",
abstract = "Normal Pressure Hydrocephalus (NPH) is one of the causes of dementia of the elderly characterized by impaired mental function, gait difficulties and urinary incontinence. Previously, it was proposed that some of the NPH patients may develop Alzheimer's disease (AD) like pathology. Aim of this study was to compare levels of different CSF biomarkers, including total secreted β-amyloid precursor protein (sAPP), sAPP-alpha form (sAPPα), amyloid-beta (Aβ) peptide, total-tau protein and hyperphosphorylated-tau protein in subjects from NPH and Non-NPH Control (NNC). CSF was collected from 23 NPH patients and 13 Non-NPH controls by lumber puncture. Western blot analysis was performed to measure levels of sAPP-total. ELISA was used separately to determine levels of sAPPα, Aβ peptide, total-tau and phospho-tau proteins. We found a significant decrease in levels of total secreted APP, sAPPα and Aβ (1-42) in the CSF sample of NPH patients vs. NNC. We did not observe any change in levels of total-tau or phospho-tau in NPH vs. NNC subjects. Notably, phospho-tau level was significantly increased in the NPH patients, who were suffering from the disease for more than one year, vs. NNC. Among five biomarkers studied, decreased sAPP, sAPPα and Aβ (1-42) levels in CSF can be molecular markers to distinguish NPH cases from NNC. Disease severity can also be assessed by increased levels of CSF phospho-tau protein and the ratio of phospho-tau to Aβ (1-42), which might be a useful tool for predicting conversion of NPH individuals to other neurodegenerative disorders including Alzheimer's disease (AD).",
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