Gene: APP

Alternate names for this Gene: AAA|ABETA|ABPP|AD1|APPI|CTFgamma|CVAP|PN-II|PN2|preA4

Gene Summary: This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene.

Gene is located in Chromosome: 21

Location in Chromosome : 21q21.3

Description of this Gene: amyloid beta precursor protein

Type of Gene: protein-coding

rs63750066 in APP gene and Alzheimer Disease, Early Onset PMID 28350801 2017 APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

PMID 23224319 2013 Distinct patterns of APP processing in the CNS in autosomal-dominant and sporadic Alzheimer disease.

PMID 25948718 2015 Homozygous carriers of APP A713T mutation in an autosomal dominant Alzheimer disease family.

PMID 19363265 2009 AbetaPP A713T mutation in late onset Alzheimer's disease with cerebrovascular lesions.

PMID 30279455 2018 Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series.

PMID 15488330 2004 Familial Alzheimer disease associated with A713T mutation in APP.

PMID 15365148 2004 A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene.

PMID 26402770 2015 Modeling the Aggregation Propensity and Toxicity of Amyloid-β Variants.

PMID 26803359 2016 Four samples were shown to be heterozygous for 1 of 3 known causative mutations: p.A713T, p.V717I, and p.V717G; this highlights the importance of screening EOAD patients for causative mutations.

PMID 1303275 1992 More missense in amyloid gene.

rs281865161 in APP gene and Alzheimer's Disease PMID 23649480 2013 Swedish mutant APP suppresses osteoblast differentiation and causes osteoporotic deficit, which are ameliorated by N-acetyl-L-cysteine.

PMID 21335619 2011 Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer's patients with the Swedish APP 670/671 mutation.

PMID 8810256 1996 Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.

PMID 27858710 2017 APP Mutations in Cerebral Amyloid Angiopathy with or without Cortical Calcifications: Report of Three Families and a Literature Review.

PMID 28350801 2017 APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

PMID 27000221 2016 Iowa APP mutation-related hereditary cerebral amyloid angiopathy (CAA): A new family from Spain.

PMID 11441013 2001 Pathogenic effects of D23N Iowa mutant amyloid beta -protein.

PMID 26402770 2015 Modeling the Aggregation Propensity and Toxicity of Amyloid-β Variants.

PMID 24878480 2014 Familial cerebral amyloid angiopathy due to the Iowa mutation in an Irish family.

PMID 26104569 2015 Iowa-type hereditary cerebral amyloid angiopathy in a Polish family.

PMID 20228223 2010 Iowa variant of familial Alzheimer's disease: accumulation of posttranslationally modified AbetaD23N in parenchymal and cerebrovascular amyloid deposits.

PMID 10656250 1999 Identification of a novel aspartic protease (Asp 2) as beta-secretase.

PMID 10677483 2000 Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein.

PMID 1678058 1991 Mis-sense mutation Val----Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease.

PMID 1415269 1992 Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region.

PMID 1671712 1991 Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

PMID 11063718 2000 Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site mutation points to an essential role for N-truncated A beta(42) in Alzheimer's disease.

PMID 10867787 2000 Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene.

PMID 11311152 2001 In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease.

PMID 1303275 1992 More missense in amyloid gene.

PMID 1465129 1992 Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production.

PMID 9754958 1998 Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation.

PMID 9328472 1997 A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43).

PMID 15365148 2004 A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene.

PMID 12034808 2002 An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala).

PMID 8577393 1995 A mutation in codon 717 of the amyloid precursor protein gene in an Australian family with Alzheimer's disease.

PMID 15201367 2004 Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease.

PMID 1302033 1992 A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid.

PMID 11528419 2001 The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation.

PMID 8267572 1993 Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease with APP717 mutations.

PMID 1303239 1992 Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene.

PMID 15201367 2004 The production and accumulation of mutated Abeta (Asn7-Abeta) or the misfunction of D678N mutant APP may have pathogenic properties for the development of Alzheimer's disease in this pedigree.

PMID 15365148 2004 This indicates that the A713T mutation of the APP gene, lying at the gamma-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.

PMID 24829003 2014 Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia: recommendations for family physicians.

PMID 20831773 2010 EFNS guidelines for the diagnosis and management of Alzheimer's disease.

PMID 21500874 2010 Preventing Alzheimer's disease and cognitive decline.

PMID 19281847 2009 Mutations in amyloid precursor protein affect its interactions with presenilin/gamma-secretase.

PMID 15776278 2005 Novel mutations and repeated findings of mutations in familial Alzheimer disease.

PMID 1925564 1991 A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.

PMID 25138979 2014 Early-onset Alzheimer's disease in two Iranian families: a genetic study.

PMID 11978821 2002 Although these data open perspectives for therapy of AD by gamma-secretase inhibition, the neuronal absence of PS1 failed to rescue the cognitive defect, assessed by the object recognition test, of the parent APP[V717I] transgenic mice.

PMID 7806491 1994 APP717 missense mutation affects the ratio of amyloid beta protein species (A beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain.

PMID 24650794 2014 Mutational analysis in early-onset familial Alzheimer's disease in Mainland China.

PMID 27838006 2017 Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer's disease.

PMID 24524897 2014 The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons.

PMID 12034808 2002 An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala).

rs63750579 in APP gene and CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED PMID 11409420 2001 Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy.

PMID 2111584 1990 Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.

PMID 16178030 2005 A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy.

PMID 20298421 2010 EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias.

PMID 20697050 2010 Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP.

PMID 12654973 2003 Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation.

rs9984764 in APP gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs2829976 in APP gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs7276737 in APP gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs9984764 in APP gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs2829976 in APP gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs2829976 in APP gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs3787629 in APP gene and Triglycerides measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.