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FB2026_01
,
released March 12, 2026
This report describes characterization of the human BACE1 gene in flies and Alzheimer disease models in Drosophila that use Hsap\BACE1 in combination with Hsap\APP. The human gene BACE1 encodes an aspartic peptidase A1 protease that is necessary for the proteolytic processing of the amyloid precursor protein (APP) to produce the amyloid beta peptide. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of Alzheimer disease patients. In Drosophila, there are related members of the aspartic peptidase A1 family, but none is a moderate- or high-scoring ortholog of BACE1. See also the human disease model report for the APP-related form of Alzheimer disease (AD1; FBhh0000119).
Multiple UAS constructs with the wild-type human Hsap\BACE1 have been generated. Pan-neuronal expression results in neuroanatomical, locomotor, and memory defects; adults exhibit reduced survival; some adults develop melanotic masses. When both Hsap\BACE1 and Hsap\APP are expressed at low levels using pan-neuronal drivers, the age-related and progressive aspects of Alzheimer disease are recapitulated.
[updated Jun. 2021 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM: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]
See general description of Alzheimer disease.
BACE1 encodes a member of the aspartic peptidase A1 family; is responsible for the proteolytic processing of the amyloid precursor protein (APP). [Gene Cards, BACE1; 2017.07.19]
Although there are related members of the aspartic peptidase A1 family in Drosophila, none is a moderate-to-high scoring ortholog of BACE1.
Many to one: 3 human to 1 Drosophila. Three human genes, APP, APLP2 and APLP1, are orthologous to the fly gene Dmel\Appl.
Ortholog of human APP (reciprocal best hit), APLP2 and APLP1 (1 Drosophila to 3 human). Dmel\Appl shares 23-25% identity and 36-42% similarity with the 3 human genes.