Preamyloid lesions and cerebrovascular deposits in the mechanism of dementia: lessons from non-beta-amyloid cerebral amyloidosis.
The importance of amyloid plaques in the pathogenesis of dementia is usually centered on beta-amyloid (Abeta) and its role in Alzheimer's disease (AD). However, since fibrillar plaques correlate poorly with neurodegeneration, challenging their importance in the mechanism(s) of dementia, investigators turned their focus to the importance of soluble oligomers and the role of preamyloid and cerebrovascular deposits. Two non-Abeta cerebral amyloidoses, familial British and Danish dementias (FBD and FDD), share many aspects of AD, including cognitive impairment and the presence of neurofibrillary tangles in limbic areas. The lack of compact plaques in FDD and in many areas in FBD further questions the importance of these lesions in the mechanism of dementia. The main components of the deposits--ABri and ADan--are structurally unrelated to Abeta and yet they all have a high tendency to oligomerize and assemble into amyloid fibrils in vitro and form ion-like channels in lipid membranes. Thus, different amyloid species have the capability to induce similar neuropathological changes, which are neither exclusive for Abeta nor dependent on the presence of compact plaques. These findings reaffirm the notion that non-Abeta amyloidoses constitute alternative models to study the role of preassembled amyloid subunits in neuronal death.
Rostagno
Agueda
A
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Ghiso
Jorge
J
D000682:Amyloid / Q000235:genetics / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000235:genetics; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003704:Dementia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D000682:Amyloid; D016229:Amyloid beta-Peptides