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FLASH GENE

Symbol

PSEN1

contributors: mct/shn - updated : 12-06-2017

HGNC name	presenilin 1
HGNC id	9508

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

ASSOCIATED DISORDERS

corresponding disease(s)

AD3 , AD6 , FTLD , CMD1U

related resource

Alzheimer Disease Mutation Database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in familial frontotemporal dementia and other atypical dementia, in dementia with Lewy bodies and variant Alzheimer's disease constitutional mosaic       somatic and germinal mosaicism in sporadic early-onset Alzheimer disease constitutional germinal mutation       in dilated cardiomyopathy, aggressive and advanced heart failure associated or not to AD

Susceptibility

putative susceptibility factor for early onset AD independent of APOE4 and for late onset AD (Alzheimer disease) to dementia with lobar atrophy and neuronal cytoplasmic inclusoions, Pick disease (OMIM: 172700)

Variant & Polymorphism	associated with the -48C->T polymorphism, in AD susceptibility and -22C->T decreases neuron specific expression of PSEN1 and increases the risk of AD
	S170F causes very-early-onsetfamilial Alzheimer disease with associated Lewy bodies
	associated with the occurrence of frontal temporal dementia
	novel PSEN1 genetic variant resulting in the substitution of a Proline with an Alanine at codon 117 (P117A)present in all demented individuals and fifty percent of at risk individuals, in early-onset Alzheimer, in the fourth decade of life (

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	PS1-/- mice have skeletal and central nervous system defects and die shortly after natural birth
	PS1/PS2 double-null mice die at embryonic day 9.5 with lack of somite segmentation, trunk ventral neural tubed disorganization, midbrain mesenchyme cell loss, anterior neuropore closure delays, and abnormal heart and second branchial arch development
	mutations in the Caenorhabditis elegans presenilin genes sel-12 and hop-1 result in a defect in the temperature memory
	mutant PS1 knockin mice primary fibroblastes exhibit a marked potentiation in the amplitude of calcium transients evoked by agonist stimulation and significant impairments in capacitative calcium entry
	neurons overexpressing mutated PS1 showed an increased vulnerability to both excitotoxic and hypoxic-hypoglycemic damage
	PS1 knockout mice or wt mice in which PS1 gene expression was knocked down by antisense treatment display reduced excitotoxic damage in neurons
	neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1(-/-) mice and the premature neuronal differentiation is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere
	inactivation of PS1 function in the adult mice cerebral cortex leads to reduced Abeta generation and subtle cognitive deficits without affecting expression of Notch downstream genes
	deleted PS1 gene in excitatory neurons of the adult mouse forebrain leads to pronounced deficiency in enrichment-induced neurogenesis in the dentate gyrus
	mice co-expressing mutant human presenilin 1 and amyloid precursor proteins display acceleration of amyloid accumulation and associative learning deficits
	conditional double knockout mice lacking both Psen1 and Psen2 in the postnatal forebrain exhibit impairments in hippocampal memory and synaptic plasticity and later develop striking neurodegeneration of the cerebral cortex
	PS1+/-PS2-/- mice develop, up to six months, an autoimmune disease characterized by dermatitis, glomerulonephritis, keratitis and vasculitis
	morpholinos directed against splice acceptor sites in zebrafish psen1 transcripts cause a hydrocephalus phenotype
	neurons in PS1-deficient mice have lysosomal acidification deficits
	PS1 deletion in blastocysts from constitutive PS1 KO mice selectively affects macroautophagic turnover of proteins, and cause defective clearance of autophagic vacuoles, defective lysosome acidification and proteolysis deficits in autolysosomes
	Ps1/Ccl2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation