Warning: Declaration of antispam_for_all_fields::addPluginSubMenu() should be compatible with mijnpress_plugin_framework::addPluginSubMenu($title, $function, $file, $capability = 10, $where = 'plugins.ph...') in C:\domains\sylics.com\wwwroot\wp-content\plugins\antispam-for-all-fields\antispam-for-all-fields.php on line 164

Warning: Declaration of antispam_for_all_fields::addPluginContent($links, $file) should be compatible with mijnpress_plugin_framework::addPluginContent($filename, $links, $file, $config_url = NULL) in C:\domains\sylics.com\wwwroot\wp-content\plugins\antispam-for-all-fields\antispam-for-all-fields.php on line 164
Alzheimer’s disease

Alzheimer’s disease

alzheimers-diseaseMouse models of Alzheimer’s disease (AD) are widely used to study amyloid-beta (Aβ) oligomerization, amyloid plaque formation and their consequences, such as Aβ-induced pathology and cognitive decline.

Alzheimer’s disease pathology

AD is a progressive, highly debilitating disease that is associated with cognitive decline. An early event in the pathology of AD is the oligomerization of Aβ and the formation of amyloid plaques. These protein aggregates, whose formation is due to an imbalance between the production of Aβ from APP, and clearance of Aβ, are thought to underlie downstream pathology, including synaptic toxicity, neurodegeneration and inflammation.

Behavioural readouts in AD models

Mouse models of AD carry human mutations that cause early-onset familial AD. These mutations lead to increased production of Aβ and a shift towards the production of Aβ42, the most toxic Aβ species. These mouse models develop amyloid plaques and severe cognitive impairments by 6 months of age (i.e. Morris Water Maze, T-maze). However, recent studies by us and others show that cognitive impairments can already be detected before plaque onset (i.e. CognitionWall™ Discrimination learning, Fear conditioning, Nesting test).

Therapeutic strategies

Various treatment options can be tested in AD mouse models. For instance, acute treatment with a BACE1 inhibitor, an enzyme critically involved in the generation of toxic Aβ species, effectively reduces the amount of Aβ42 in brain tissue a few hours after treatment. In addition to the analysis of Aβ levels in the brain, cerebrospinal fluid, and blood using ELISA, the number and size of amyloid plaques can be quantified after immunohistochemical staining of brain slices of mouse models of AD.

Available AD models

The available models include, but are not limited to:
The APPswe model was originally developed in the laboratory of Karen Hsiao at the University of Minnesota, in association with the Mayo Clinic. This model was created by microinjecting the human APP695 gene containing the double mutation K670N, M671L into B6SJLF2 zygotes using a hamster prion protein cosmid vector.
The JNPL3 Tau model was originally developed in the laboratory of Mike Hutton at the Mayo Clinic. The model was created by microinjecting transgenic constructs containing the P301L mutation of the microtubule associated tau gene and mouse prion promoter into B6D2F1 x SW zygotes.
The APOE4 model was developed in the laboratory of Nobuya Maeda at the University of North Carolina. The model was created by targeting the murine Apoe gene for replacement with the human APOE4 allele in E14TG2a ES cells and injecting the targeted cells into blastocysts.
The Aβ Oligomer (ABO) induced model is based on the intracranial infusion of proprietary Aβ oligomers.
Please inquire at info@sylics.com the suitability of the above models for your research question, as well as additional models.