title: A possible role for CSF turnover and choroid plexus in the pathogenesis of late onset Alzheimer's disease.
abstract: According to the amyloid theory, the appearance of amyloid-β (Aβ) deposits represents a pivotal event in late onset Alzheimer's disease (LOAD). Physiologically, Aβ42 monomers are cleaned by capillary resorption, enzymatic catabolism, and cerebrospinal fluid (CSF) transport. Factors that promote the oligomerization of Aβ42 must be specified. In vitro, these monomers spontaneously form neurotoxic oligomers whose rate increases with time suggesting that the stasis of CSF favors the oligomerization. In animals, experimental hydrocephalus generates CSF stasis followed by the appearance of amyloid deposits. In normal pressure hydrocephalus, amyloid deposits are common, especially in elderly patients, and the turnover decline has the same order of magnitude as in AD. In this disease, the effects of CSF stasis are potentiated by the decline in the ability of CSF to inhibit the formation of oligomers. CSF originates from choroid plexus (CP). In LOAD, the functions of secretion, synthesis, and transport of CP are impaired and this is related to morphological modifications. These impairments favor the decrease of CSF turnover, the diminished levels of transthyretin, a sequestering protein synthesized by CP, and the oligomerization of Aβ42. They are potentiated by a reduced enzymatic catabolism and a decreased capillary reabsorption of Aβ42, both alterations being related to age.
authors.affiliation: Department of Geriatry, CHU Amiens, Amiens Cedex 1, France. serot.jean-marie@chu-amiens.fr
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Serot
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Zmudka
authors.forename: Pierre
authors.initials: P
authors.lastname: Jouanny
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D002831:Choroid Plexus / Q000473:pathology*; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D058225:Plaque, Amyloid
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)