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

• Published in: Journal of psychiatric research Vol. 45; no. 4; pp. 539 - 547
• Main Authors: Ray, Balmiki, Reyes, Patricio F, Lahiri, Debomoy K
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.04.2011; Elsevier
• Subjects: Alzheimer's disease; Amyloid beta-peptide; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Protein Precursor - cerebrospinal fluid; Biological and medical sciences; Biological markers; Cerebrospinal fluid; Cerebrospinal fluid. Meninges. Spinal cord; Clearance; Disease progression; Enzyme-Linked Immunosorbent Assay - methods; Female; Humans; Hydrocephalus, Normal Pressure - cerebrospinal fluid; Indexing in process; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; NPH; Pathology; Peptide Fragments - cerebrospinal fluid; Phosphorylation; Precursors; Proteins; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Statistics, Nonparametric; Suffering; Tau; tau Proteins - cerebrospinal fluid; Tau; Amyloid beta-peptide; Cerebrospinal fluid; Clearance; NPH; Disease progression; Disease development; Human; Nervous system diseases; Normal pressure hydrocephaly; Amyloid precursor protein; Cerebral disorder; Tau protein; β Amyloid protein; Central nervous system disease
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2010.07.011

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).