Background: Function of the Amyloid Precursor Protein (AβPP) and its various cleavage
products still is not unraveled down to the last detail. While its role as a source of the neurotoxic Amyloid
beta (Aβ) peptides in Alzheimer’s Disease (AD) is undisputed and its property as a cell attachment
protein is intriguing, while functions outside the neuronal context are scarcely investigated. This is particularly
noteworthy because AβPP has a ubiquitous expression profile and its longer isoforms,
AβPP750 and 770, are found in various tissues outside the brain and in non-neuronal cells.
Objective: Here, we aimed at analyzing the 5xFAD Alzheimer’s disease mouse model in regard to male
sexual function. The transgenes of this mouse model are regulated by Thy1 promoter activity and Thy1
is expressed in testes, e.g. by Sertoli cells. This allows speculation about an influence on sexual behavior.
Methods: We analyzed morphological as well as biochemical properties of testicular tissue from 5xFAD
mice and wild type littermates and testosterone levels in serum, testes and the brain. Sexual behavior
was assessed by a urine scent marking test at different ages for both groups.
Results: While sperm number, testes weight and morphological phenotypes of sperms were nearly indistinguishable
from those of wild type littermates, testicular testosterone levels were significantly increased
in the AD model mice. This was accompanied by elevated and prolonged sexual interest as displayed
within the urine scent marking test.
Conclusion: We suggest that overexpression of AβPP, which mostly is used to mimic AD in model
mice, also affects male sexual behavior as assessed additional by the Urine Scent Marking (USM) test.
The elevated testosterone levels might have an additional impact on central nervous system androgen
receptors and also have to be considered when assessing learning and memory capabilities.