Biomaterial Database

Genetic aspects of amyloid beta-protein fibrillogenesis in Alzheimer's disease. 2004

Anna Kowalska

Institute of Human Genetics, Polish Academy of Sciences, Poznań. annkowal@rose.man.poznan.pl

Although deposition of aggregated amyloid beta-protein (Abeta) in human brain is a fundamental pathological event in the development of Alzheimer's disease (AD), our knowledge of the molecular mechanisms underlying the initiation of Abeta fibril formation remains still very incomplete. Recent data indicate that genetic factors have a direct effect on Abeta fibrillogenesis. Most of pathogenic mutations identified in genes responsible for familial AD (FAD) affect activities of alpha-, beta, and gamma-secretases during amyloid precursor protein (APP) processing leading to a significant increase in the Abeta42/Abeta40 concentration ratio. The enhanced anabolism of Abeta may lead to its deposition. Recently, it was shown that the two main alloforms of Abeta have distinct biological activity and behaviour at the earliest stage of assembly. In vitro studies showed that Abeta42 monomers, but not Abeta40, form initial and minimal structures (pentamer/hexamer units called paranuclei), which can oligomerise to larger forms. This finding may explain the particularly strong association of Abeta42 with AD. We have reviewed molecular effects of APP and Presenilin mutations responsible for FAD in both Abeta metabolism and formation of Abeta fibril.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544	Alzheimer Disease	A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)	Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D016229	Amyloid beta-Peptides	Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.	Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016564	Amyloid beta-Protein Precursor	A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.	Amyloid A4 Protein Precursor,Amyloid Protein Precursor,beta-Amyloid Protein Precursor,Amyloid beta Precursor Protein,Protease Nexin 2,Protease Nexin II,Amyloid beta Protein Precursor,Nexin 2, Protease,Nexin II, Protease,beta Amyloid Protein Precursor,beta-Protein Precursor, Amyloid