Cerebrospinal fluid transthyretin: aging and late onset Alzheimer's disease

摘要

The deposition of insoluble β-amyloid protein fibrils isprobably the central event in the pathogenesis of Alzheimer's disease. Cerebrospinal fluid inhibits this fibril formation, likely by theintervention of one or several proteins binding to soluble β-amyloidprotein. In vitro, transthyretin (TTR), a CSF protein, impedes amyloidfibrillogenesis. Lowered concentrations of CSFTTR couldtherefore be associated with Alzheimer's disease. Concentrations ofTTR in CSF samples from 149 consecutive patients wereassayed, using a kinetic nephelemetric method. These concentrationswere correlated positively with age, but were significantly lower in patients with Alzheimer's disease. These data raise the possibility that amyloid fibril formation could be promoted in patients with lateonset Alzheimer's disease by the lack of sufficient concentrations of TTR.