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.
[updated Aug. 2019 by FlyBase; FBrf0222196]