Abnormal cerebrospinal fluid (CSF) dynamics in Alzheimer's disease and normal pressure hydrocephalus: CSF-amyloid β precursor protein metabolites as possible biomarkers

摘要

In this issue, Miyazima et al. examined cerebrospinal fluid (CSF) samples from 46 idiopathic normal pressure hydrocephalus (iNPH) patients, 10 Alzheimer's disease (AD) patients, and eight non-demented controls for biochemical correlates potentially involved in neurodegeneration [1]. They assayed levels of amyloid β (Aβ) precursor protein (APP) metabolites and tau proteins (total and phosphorylated isoform) and observed significant differences in CSF levels of phosphorylated tau and APP metabolites in the non-demented controls versus either iNPH or AD patients. APP is a transmembrane protein and is cleaved by α or β secretases to yield sAPPα and sAPPβ, respectively [2, 3]. Processing of APP by β secretase also produces Aβ peptides with varying amino acid residues (Aβ40 and Aβ42), which are found to be aberrantly deposited in the brain of patients with AD. Processing of APP by α secretase precludes Aβ generation and is hence believed to be ‘non-amyloidogenic’. The present work is significant because CSF Aβ and phosphorylated tau profiles are important antemortem protein biomarkers in AD [4, 5] and may potentially be for iNPH. Although these biomarkers in patients with AD showed variable sensitivity and specificity, studies with the same in the iNPH patients are relatively scanty, and the present work bridges this gap of knowledge.