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 P-amyloid (Abeta) peptide and intracellularly by tau protein. The disease presents several major diapostic 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. (C) 2002 Elsevier Science Ltd. All rights reserved.