Cerebrospinal Fluid Markers of Alzheimer's Disease

Abstract

Objective: To review studies on cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) in order to answer the question whether CSF contains a specific marker which can be used to support a clinical diagnosis of AD. Data sources: Studies identified through an English‐language literature search using MEDLINE (1966 to 1990) and a review of bibliographies of relevant articles. Study Selection: All studies on CSF in AD patients were selected. Double publications on the same original data were not included. Otherwise, no particular selection was made. Data Extraction: The diagnostic utility of more than 60 substances, including CSF measures related to classical neurotransmitters, (neuro)peptides, proteins, amino acids, purines, trace elements, and constituents of senile plaques and neurofibrillary tangles, is evaluated. Clinical epidemiological criteria for deciding on the usefulness of new diagnostic methods are emphasized in this analysis. Data Synthesis: Concentrations of some CSF constituents are consistently found to be significantly changed in AD. However, overlap with data of control populations and methodological shortcomings in study design, limit the diagnostic value of all CSF measurements reviewed. Conclusion: None of the CSF constituents studied so far can be used in support of the diagnosis of AD. However, increased knowledge concerning macromolecular abnormalities in amyloid containing plaques and neurofibrillary tangles makes the outlook for a diagnostic test for AD on CSF promising.

Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer's Disease (AD): A Meta-Analysis of CSF Markers

“…For the antioxidant glutathione (GSH), 13 publications were rejected [ 35 - 47 ]. For the amino acids, 20 publications were rejected [ 41 , 48 - 67 ]. Last, for the metabolites/neurotransmitters 14 publications were rejected [ 5 , 58 , 68 - 78 ].…”

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

“…Until the identi¢cation of tau and Ab 42 proteins in CSF, these attempts were destined for the dustbin. 114 However, the many studies aimed at quanti¢cation of both tau and Ab 42 in CSF have demonstrated that their analysis may contribute to the di¡erential diagnostic work-up of dementia syndromes, especially in the identi¢cation of AD patients. Recommendations made by an international consensus group state that the sensitivity for the ideal AD biomarker should exceed 80% with a speci¢city of distinguishing other dementia syndromes of more than 80% as well.…”

Detection of glutamine synthetase in the cerebrospinal fluid of Alzheimer diseased patients: a potential diagnostic biochemical marker.

“…Several studies have focused on the cerebrospinal fluid (CSF) for the presence ofa biochemical change that may be a diagnostic marker for AD (reviewed in ref. 3). Amyloid, paired helical filament, and a1-antichymotrypsin immunoreactivity have been reported to be elevated in the CSF of AD patients (4)(5)(6).…”