This report describes Alzheimer disease 4 (AD4), which is a subtype of Alzheimer disease; AD3 exhibits an autosomal dominant pattern of inheritance. The human gene implicated in this disease is PSEN2 (Presenilin 2), the catalytic component of a gamma-secretase complex. Gamma-secretase is responsible for proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. PSEN2 is also implicated in dilated cardiomyopathy 1V (CMD1V, FBhh0000155). There is a single fly ortholog of PSEN2, 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 PSEN1 (see report for AD3, FBhh0000120).
Multiple different UAS constructs of the human gene Hsap\PSEN2 have been introduced into flies, including wild-type PSEN2 and genes carrying mutational lesions implicated in AD4. Variant(s) implicated in human disease (as transgenic human gene, PSEN2): M239V and N141I variant forms of the human gene have been introduced into flies, but have not been characterized to date.
[updated Aug. 2019 by FlyBase; FBrf0222196]