Metabolic defects in Alzheimer's disease (AD)

Alzheimer's disease remains a largely untreated condition. Current treatments only target symptoms and hence are merely palliative. Development of effective treatments relies on identifying the underlying factors that give rise to the clinical symptoms of the disease. One such set of targets is the well characterized defects in lipid and glucose metabolism associated with AD. Accera is developing novel therapies that target these metabolic defects and may lead to new treatments for this devastating disease.

The main fuel for the brain is the sugar glucose. In neuronal cells, glucose is used both to generate energy and to produce cellular factors such as cholesterol and acetylcholine. Neuronal cells do not efficiently utilize fats, therefore decreases in glucose uptake or utilization will have broad deleterious consequences in these cells. Low glucose levels will result in disturbances in cholesterol homeostasis, cholinergic defects, and altered processing and clearing of cellular proteins - all of which are physiological hallmarks of AD. For example, disturbances in cholesterol metabolism are known to affect the processing of the Amyloid Precursor Protein (APP). Mutations in the APP gene have been identified as causal in some cases of early onset AD, and altered processing of APP is found in both early and late onset AD.

Regional defects in glucose utilization have been well documented in AD and can be detected in at-risk populations, as early as 40 years of age, decades before clinical symptoms arise. The cause of the decreased glucose metabolism remains uncertain, but may be related to disturbances in lipid metabolism. Membrane proteins, such as glucose transporters, rely on specific lipid environments in which to function. If these environments are not ideal, glucose transporters and other membrane proteins function poorly. Hence, altered lipid metabolism may be at the heart of AD. This model is consistent with the lipid transport gene, Apolipoprotein E, as the major risk factor developing the most common form of AD.

Accera has developed novel treatments to alleviate both defects in glucose utilization and lipid metabolism. These treatments are designed to increase energy to neuronal cells and provide raw materials for cholesterol and acetylcholine synthesis. Accera's revolutionary approach is unique among companies developing treatments for AD.

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