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General Information
Name
Alzheimer disease, presenilin-related
FlyBase ID
FBhh0000623
Disease Ontology Term
Parent Disease
OMIM
Overview

Two forms of early-onset familial Alzheimer disease are associated with presenilin genes in human: PSEN1 is implicated in Alzheimer disease 3 (AD3, FBhh0000120) and PSEN2 is implicated in Alzheimer disease 4 (AD4, FBhh0000121). Both AD3 and AD4 exhibit autosomal dominant inheritance. There is a single presenilin in Drosophila, Dmel\Psn, for which classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Presenilin is the catalytic component of the gamma-secretase complex. Gamma-secretases (γ-secretases) are transmembrane multiprotein complex comprised of presenilin (PSEN1 or PSEN2), nicastrin (NCSTN), PSENEN, and APH1 (APH1A or APH1B); gamma-secretases are responsible for intramembrane proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. See also the human disease model report 'Alzheimer disease, susceptibility to (postulated), NCSTN-related' (FBhh0000836).

Multiple different UAS constructs of both human genes, Hsap\PSEN1 and Hsap\PSEN2 have been introduced into flies, including wild-type and genes carrying mutational lesions implicated in Alzheimer disease. They have been characterized for interactions using a fly model of Alzheimer disease 1 (FBhh0000119).

In flies, it appears that levels of expression of Dmel\Psn need to be within a precise range: homozygous loss-of-function mutations in the Psn gene are lethal; heterozygous animals develop age-related cognitive defects; overexpression of wild-type Psn is also deleterious. RNAi-effected knockdown of Psn in selected neurons of the adult brain results in shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration; similar phenotypes are observed for RNAi-effected knockdown of Nct in comparable experiments. Physical and genetic interaction(s) of Dmel\Psn have been described; see below and in the gene report for Psn.

[updated Jul. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: Alzheimer disease, presenilin-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
Gamma-secretase is a transmembrane multiprotein complex comprised of presenilin (PSEN1 or PSEN2), nicastrin (NCSTN), PSENEN, and APH1 (APH1A or APH1B); it is responsible for intramembrane proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. [from OMIM:104311; 2018.07.09]
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)
Many to one: 2 human to 1 Drosophila. Two human genes, PSEN1 and PSEN2, are orthologous to the fly gene Dmel\Psn.
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)
Many to one: 2 human to 1 Drosophila. Two human genes, PSEN1 and PSEN2, are orthologous to the fly gene Dmel\Psn.
Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    In progress.Contributions welcome.
    Gene Groups / Pathways
    Comments on ortholog(s)
    Ortholog of human genes PSEN2 and PSEN1 (1 Drosophila to 2 human). Dmel\Psn shares 47-48% identity and 59-62% similarity with the 2 human genes.
    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (7 groups)
    protein-protein
    Interacting group
    Assay
    References
    ubiquitin reconstruction
    anti tag coimmunoprecipitation, anti tag western blot, western blot, anti bait coimmunoprecipitation
    anti tag coimmunoprecipitation, anti tag western blot
    molecular sieving, western blot
    anti tag coimmunoprecipitation, western blot, molecular sieving
    anti tag coimmunoprecipitation, anti tag western blot
    pull down, anti tag western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (16 alleles)
    Models Based on Experimental Evidence ( 13 )
    Modifiers Based on Experimental Evidence ( 7 )
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
    Allele class
    Mutagen
    Publicly Available Stocks
    ethyl methanesulfonate
    loss of function allele
    ethyl methanesulfonate
    loss of function allele
    ethyl methanesulfonate
    Delta2-3 transposase
    loss of function allele
    ethyl methanesulfonate
    loss of function allele
    ethyl methanesulfonate
    Delta2-3 transposase
    loss of function allele
    ethyl methanesulfonate
    References (22)