title: Genetics and pathology of alpha-secretase site AbetaPP mutations in the understanding of Alzheimer's disease.
abstract: Development of therapeutics begins with delineating the precise disease pathology along with a reasonable understanding of the sequence of events responsible for the development of disease, or disease pathogenesis. For Alzheimer's disease (AD), the classical pathology is now known for quite some time; however, the disease pathogenesis has eluded our understanding for a complete century. This review, in addition to providing a brief overview of all primary events, will highlight those aspects of AD genetics and novel pathological descriptions linked to unique mutations within AbetaPP that have led to our better understanding of the pathogenesis of AD. Specifically, we will discuss how pathologies linked to the Dutch (E693Q) and Flemish AbetaPP (A692G) mutations have helped in understanding the role of CAA in dementia and in the development of dense-core plaques. In addition, this review will also point directions that warrant additional studies.
authors.affiliation: Department of Molecular Genetics, Neurodegenerative Brain Diseases Research Group, Flanders Interuniversity Institute for Biotechnology, Institute Born-Bunge and University of Antwerp, Antwerpen, Belgium. christine.vanbroeckhoven@ua.ac.be
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Samir
authors.initials: S
authors.lastname: Kumar-Singh
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites / Q000502:physiology*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D053764:Presenilin-1
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human