Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer’s disease patients

Abstract

Immunoreactivities of total apolipoprotein E (ApoE-IR), amyloid beta peptide(1-42) (Abeta42-IR), interleukin-6 (IL-6-IR), substance P (SPIR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid samples of patients with Alzheimer's disease (AD), non-Alzheimer's dementias (NAD), neurological disorders without cognitive impairment (OND) and controls without central nervous system disease using sensitive and specific enzyme immunoassay methods. TTIR was highly significantly increased (P < 0,001) and Abeta42-IR was significantly decreased (P < 0,001 vs. OND/CO, P < 0,03 vs. NAD) in the AD cohort compared with the other diagnostic groups. Significant increases in AD were also found for ApoE-IR (P < 0,001) and IL-6 (P < 0,03), but there was a considerable overlap between groups. In the total AD cohort, SPIR was not significantly changed, but AD patients with late disease onset (>65 years) showed significantly higher values than both early onset patients (<65 years) and controls (P < 0,05). Discriminant function analysis showed that Abeta42-IR (cut-off value 375pg/ml) and TTIR (cut-off value 440 pg/ml) levels contributed most to the group classification of patients. At 85% sensitivity for AD and 100% specificity for controls, the combined evaluation of Abeta42-IR and TTIR in this cross-sectional study resulted in a graph separating AD from non-AD patients with increased specificity of 91% and 75% for AD versus OND and NAD, respectively.

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

“…It is characterized by the formation of neurofibrillary tangles in the cortex, which are mainly constituted by altered phosphorylated and truncated portions of tau protein and by abnormal extracellular deposition of neurotoxic beta amyloid (Aβ) peptides 46 . Reduced SP levels were found in cortical regions of post-mortem brain tissues of patients suffering from AD 47,48 but conflicting results were obtained regarding SP levels in the CSF, where they were elevated or reduced depending on the study [49][50][51] . Transgenic mouse models of AD based on the known genetic origins of familial AD have significantly contributed to the understanding of the molecular mechanisms involved in the onset and progression of the disease 52 .…”

Markers of inflammation and cognitive decline in an African‐Caribbean population

“…Inflammatory processes may play an important role in late-life cognitive decline. Widespread immunoreactivity for inflammatory factors has been found in senile plaques and neurofibrillary tangles associated with Alzheimer's disease (AD) (Iwamoto et al, 1994), as well as increased serum and cerebrospinal fluid concentrations of inflammatory factors (Maes et al, 1999;Rosler et al, 2001). …”

CSF biomarkers in different phenotypes of Parkinson disease

“…Centrifuged CSF samples were frozen at -80°C. Examination of lumbar CSF was performed using ELISA methods for Ab-42 and total tau (TT) immunoreactivity (Innogenetics, Belgium)-for methods see Rösler et al (2001). The storage time between CSF collection and analysis ranged from 10-60 days (mean 30.5 ± 3.0).…”