Basic Science and Pathogenesis.

Background: Alzheimer's Disease research lacks a suitable model to match the sporadic version of Alzheimer's Disease (SAD). We a propose a model that will use 7PA2 cells which is a CHO modified to express the V717F mutation for APP (Indiana mutation). The 7PA2 cells will then be placed inside alginate microbeads to produce a factory that constantly produces amyloid species.

Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease.

According to the amyloid cascade hypothesis, the earliest trigger in the development of Alzheimer's disease (AD) is the accumulation of toxic amyloid-β (Aβ) fragments, eventually leading to the classical features of the disease: amyloid plaques, neurofibrillary tangles and synaptic and neuronal loss. The lack of relevant non-transgenic preclinical models reflective of disease progression is one of the main factors hindering the discovery of effective drug treatments. To this end, we have developed a protocol for the fabrication of alginate microbeads containing amyloid-secreting cells useful for the study of the effects of chronic Aβ production.

Stabilized Low-n Amyloid-β Oligomers Induce Robust Novel Object Recognition Deficits Associated with Inflammatory, Synaptic, and GABAergic Dysfunction in the Rat.

Background: With current treatments for Alzheimer's disease (AD) only providing temporary symptomatic benefits, disease modifying drugs are urgently required. This approach relies on improved understanding of the early pathophysiology of AD. A new hypothesis has emerged, in which early memory loss is considered a synapse failure caused by soluble amyloid-β oligomers (Aβo).