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General Information
Name
Alzheimer disease 3
FlyBase ID
FBhh0000120
Disease Ontology Term
Parent Disease
Overview

This report describes Alzheimer disease 3 (AD3), which is a subtype of Alzheimer disease; AD3 exhibits an autosomal dominant pattern of inheritance. The human gene implicated in this disease is PSEN1 (Presenilin 1), the catalytic component of a gamma-secretase complex. Gamma-secretase is responsible for proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. PSEN1 is implicated in several other human diseases (see OMIM:104311), including frontotemporal dementia (FTD, FBhh0000809), Pick disease (FBhh0000112), and dilated cardiomyopathy 1U (CMD1U, FBhh0000154). There is a single fly ortholog of PSEN1, Dmel\Psn, for which classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Psn is also orthologous to the human gene PSEN2 (see report for AD4, FBhh0000121).

Multiple different UAS constructs of the human gene Hsap\PSEN1 have been introduced into flies, including wild-type and genes carrying mutational lesions implicated in AD3. Variant(s) implicated in human disease (as transgenic human gene, PSEN1): M146V and P267S variant forms of the human gene have been introduced into flies, but have not been characterized to date. Variant(s) implicated in human disease (as transgenic human gene, PSEN1): deletion of exon 9 (ΔE9); two implicated variants in human populations, a splice site mutation and a genomic deletion, result in deletion of exon 9; this ΔE9 variant has been investigated in Drosophila.

For data concerning disease models using the fly Psn gene, see the report for 'Alzheimer disease, presenilin-related' (FBhh0000623).

[updated Aug. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Alzheimer disease
Symptoms and phenotype
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from OMIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Specific Disease Summary: Alzheimer disease 3
OMIM report
[ALZHEIMER DISEASE 3; AD](https://omim.org/entry/607822)
Human gene(s) implicated
[PRESENILIN 1; PSEN1](https://omim.org/entry/104311)
Symptoms and phenotype
Alzheimer disease 3 (AD3) is characterized by typical symptoms of Alzheimer disease (described above).
Genetics
Alzheimer disease 3 is inherited as an autosomal dominant; it is associated with heterozygous mutations in the PSEN1 gene. [from OMIM:607822; 2016.01.08]
Cellular phenotype and pathology
Molecular information
The PSEN1 gene encodes presenilin-1, which forms the catalytic component of a gamma-secretase complex. Gamma-secretase is responsible for proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. Gamma-secretase is a multiprotein complex containing PSEN1 or PSEN2 and multiple other components. [from OMIM:104311; 2016.01.08]
External links
Disease synonyms
AD3
Alzheimer disease, familial, 3
Alzheimer disease 3, early-onset
Alzheimer disease, early-onset
early-onset familial Alzheimer disease
eFAD
EOFAD
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.
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 (11)