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FLASH GENE

Symbol

APP

contributors: shn - updated : 05-12-2019

HGNC name	amyloid beta (A4) precursor protein
HGNC id	620

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

ASSOCIATED DISORDERS

corresponding disease(s)

AD1 , HCHWAD

related resource

Alzheimer Disease Mutation Database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in cerebral hemorrhage due to congophilic amyloid angiopathy (CAA) with periventricular and subcortical white matter lesions at young age constitutional     --low   in autism with duplicated UBE3A constitutional       loss of function inhibition of APP ferroxidase activity may contribute to neuronal iron accumulation in Alzheimer cortex, and elevated brain iron is a complication of aging constitutional     --other   in FRA X fibroblasts, a dual dysregulation of APP and ADAM10 leads to the production of an excess of soluble APPalpha and to synaptic and behavioral deficits

Susceptibility

to schizophrenia to Alzheimer disease

Variant & Polymorphism other	mutation APP692
	APP-promoter mutations that significantly increase APP expression levels are associated with AD
	association between rs463946 (-3102 G/C) and AD
	mutation (A673T) in the APP gene that protects against Alzheimer disease and cognitive decline in the elderly without Alzheimer disease

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer postmenopausal estrogen (17beta-estradiol) replacement therapy may prevent or delay the onset of AD

ANIMAL & CELL MODELS

	transgenic mouse models expressing human Alzheimer's A beta peptide exhibit brain regions severely affected in Alzheimer's disease resulting in extensive neuronal degeneration (LaFerla 1995)
	double mutant (tau/APP) mice exhibited neurofibrillary tangle pathology substantially enhanced in the limbic system and olfactory cortex (Lewis 2001)
	co-expression of both mutant transgenes presenilin 1 and APP results in acceleration of amyloid accumulation and associative learning deficits (Dineley 2002)
	expression of human Abeta42 peptide in the Drosophila brain led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration and Abeta40 caused only age-dependent learning defects (Iijima 2004)
	FVB/N mice overexpressing human APP695 develop a central nervous system disorder and die prematurely, precluding development of Abeta peptide amyloid plaques whereas 129S6 mice are resistant to the lethal effects of APP overexpression (Krezowski 2004)
	gene expression analysis revealed that the genes related to mitochondrial energy metabolism and apoptosis were up-regulated in 2-month-old Tg2576 mouse AD model and that the same genes were up-regulated at 5 and 18 months of age suggesting that mitochondrial energy metabolism is impaired by the expression of mutant APP and/or Abeta, and that the up-regulation of mitochondrial genes is a compensatory response (Reddy 2004)
	estrogen-deficient APP23 mice exhibited greatly reduced brain estrogen, early-onset and increased beta amyloid peptide (Abeta) deposition and increased Abeta production (Yue 2005)
	memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly suggesting that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease (Lesné 2006)
	Lack of NO synthase 2 in the amyloid precursor protein Swedish mutant mouse increased insoluble beta-amyloid peptide levels, neuronal degeneration, caspase-3 activation, and tau cleavage (Colton 2006)
	Alzheimer disease mice deficient in Ccr2 accumulated Abeta earlier and died prematurely. Ccr2 deficiency accelerates early disease progression and markedly impairs microglial accumulation (El Khoury 2007)