Alzheimer’s disease

Alzheimer’s disease pathology

The hallmarks of Alzheimer’s disease seen in post-mortem brain tissue of patients are extracellular deposits of amyloid beta (plaques) and intracellular inclusions of the protein tau (tangles). An early event in the pathology of Alzheimer’s disease (AD) is the oligomerization of Aβ and the formation of amyloid plaques. These oligomers and aggregates are thought to underlie, at least in part, downstream pathology including tau misfolding, synaptic toxicity and inflammation. Evidence from postmortem studies shows that tau pathology in Alzheimer’s disease starts in the entorhinal cortex and spreads throughout the brain. Recent PET studies show that the increase in tau pathology correlates well with the decline in cognitive function seen in Alzheimer’s disease patients.

Risk factors

Although amyloid and tau remain the most widely studied proteins in the context of Alzheimer’s disease, risk factors and associated pathways are increasingly recognized as valuable therapeutic targets. The largest genetic risk factor for late onset Alzheimer’s disease is genetic variation in the gene coding for Apolipoprotein E (APOE). APOE is a protein involved in the metabolism of fats. Carriers of the APOE4 allele have a 3 to 12 fold increased risk to develop Alzheimer’s disease. Furthermore, epidemiological studies have implicated metabolic syndrome and type 2 diabetes as risk factors for cognitive decline and Alzheimer’s disease.

Available AD modelsbiotechnical-services

Sylics offers fee-for-service studies in transgenic amyloid models, transgenic tau models and a tau seeding model. The Aβ Oligomer (ABO) induced model is based on the intracranial infusion of proprietary Aβ oligomers. With respect to risk factors, Sylics offers studies in the APOE4 model. Sylics is currently optimizing a type 2 diabetes model of cognitive dysfunction. Please inquire at the suitability of the above models for your research question, as well as additional models.