Pathogenic theories and intrathecal analysis of the sporadic form of Alzheimer's disease.
Alzheimer's disease (AD) is an age-dependent dementia characterized by progressive loss of cognitive functions and by characteristic pathological changes in the brain: the formation of aggregates extracellularly by beta-amyloid (Abeta) peptide and intracellularly by tau proteins. The disease presents several major diagnostic difficulties: (1) AD develops slowly; (2) analysis of damaged brain tissues is difficult, requiring a biopsy which poses ethical problems; (3) no biochemical markers are available for the diagnosis and monitoring of the disease progression. Since the cerebrospinal fluid (CSF) is in contact with the extracellular space of the brain, many studies have tried to correlate the levels of the intrathecal peptides and amino acids and the development of dementia. The present review analyzes the main results of intrathecal content analyses in light of pathogenic theories proposed to explain the damage associated with AD and observed in the brain of patients by postmortem examination.
Torreilles
François
F
CNRS UMR 5094, Institut de Biotechnologie et Pharmacologie, UFR Pharmacie, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France. ftorreilles@yahoo.fr
Touchon
Jacques
J
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001120:Arginine / Q000172:deficiency; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002118:Calcium / Q000172:deficiency; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000172:deficiency; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D009435:Synaptic Transmission; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D002556:Cerebrospinal Fluid Proteins; D007527:Isoenzymes; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D030421:Peroxynitrous Acid; D001708:Biopterins; D001120:Arginine; D019001:Nitric Oxide Synthase; C003402:sapropterin; D002118:Calcium