title: The role of vascular factors in late-onset sporadic Alzheimer's disease. Genetic and molecular aspects.
abstract: Alzheimer's disease (AD) is a late-onset progressive neurodegenerative disorder which results in the irreversible loss of cortical neurons, particularly in the associative neocortex and hippocampus. AD is the most common form of dementia in the elderly. Apart from the neuronal loss, the pathological hallmarks are extracellular senile plaques, containing the peptide beta-amyloid (Abeta), and neurofibrillary tangles. The Abeta cascade hypothesis remains the main pathogenetic model, as suggested by familiar AD, mainly associated to mutation in amyloid precursor protein and presenilin genes. The remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmental conditions and genetic features of the individual. A relationship between genetic and acquired vascular factors and AD has been hypothesized. Many vascular risk factors for AD, such as atherosclerosis, stroke and cardiac disease in the aging individual, could result in cerebrovascular dysfunction and trigger AD pathology. A major vascular susceptibility factor gene is the apolipoprotein E gene, found to be associated with sporadic late-onset AD cases. Another interesting vascular susceptibility gene is angiotensin converting enzyme. Other possible genes include VLDL-R, LRP, NOS3, CST3, OLR1, MTHFR, PON1 and VEGF, but many of the related studies have shown conflicting results. In this paper, we review the role of molecular vascular abnormalities and of the "vascular risk" genes supposed to be involved in the pathogenesis of AD, in an attempt to provide a comprehensive picture of what is known about the mechanisms underlying the role of vascular factors in late-onset sporadic AD.
authors.affiliation: Department of Neuroscience, Neurological Clinic, University of Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rocchi
authors.forename: D
authors.initials: D
authors.lastname: Orsucci
authors.forename: G
authors.initials: G
authors.lastname: Tognoni
authors.forename: R
authors.initials: R
authors.lastname: Ceravolo
authors.forename: G
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008954:Models, Biological; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C021266:vascular factor