Methods of diagnosing alzheimer's disease and risk of progression to alzheimer's disease

Inventors

Soriano, Salvador • Castello, Michael

Assignees

Loma Linda University

Abstract

In one aspect, methods of diagnosing a subject as having Alzheimer's disease and prognosing a subject as being at risk of progressing to Alzheimer's disease are provided. In some embodiments, the method comprises determining one or more of the level of expression of rhotekin 2 (RTKN2), the level of expression of microtubule-associated Ser/Thr kinase 4 (MAST4), the level of binding of forkhead box O1 (FOXO1) to the RTKN2 promoter, and the level of binding of amyloid precursor protein (APP) to the MAST4 promoter in a sample from the subject.

Core Innovation

The invention provides methods for diagnosing and prognosing Alzheimer's disease by detecting specific biomarkers in a subject's sample. In particular, the methods involve measuring one or more of the expression levels of rhotekin 2 (RTKN2) and microtubule-associated Ser/Thr kinase 4 (MAST4), as well as the binding activity of forkhead box O1 (FOXO1) to the RTKN2 promoter and amyloid precursor protein (APP) to the MAST4 promoter. The assessment of these markers, either individually or in combination, allows for the determination of Alzheimer's disease presence or risk of progression.

The problem addressed by this invention is the lack of reliable diagnostic methods for Alzheimer's disease that can detect the disease early and provide minimally invasive procedures. Existing approaches, primarily based on amyloid-beta accumulation, have failed to consistently treat or identify Alzheimer's disease, especially since amyloid-beta is neither necessary nor sufficient to trigger the disease. There is a pronounced need for more effective biomarkers and diagnostic strategies that can accurately detect Alzheimer's disease or gauge the risk of its progression.

The solution proposed involves detecting decreased expression of RTKN2 and MAST4, increased binding of FOXO1 to the RTKN2 promoter, and decreased binding of APP to the MAST4 promoter as indicators of Alzheimer's disease. These molecular signatures can be assayed from blood, serum, plasma, or cerebrospinal fluid, providing a less invasive diagnostic option. The invention further includes methods for prognosing at-risk patients (such as those with Mild Cognitive Impairment) and suggests the potential for therapeutic interventions based on the detected biomarker profiles, including lipid-lowering medications or compounds enhancing RTKN2 expression.

Claims Coverage

The independent claim covers a method for treating a subject by delaying or reversing Alzheimer's disease progression via biomarker measurement and therapeutic intervention. The dependent claims expand on this by incorporating detection of additional biomarkers and methods for establishing reference values.

In summary, the claims are focused on a therapeutic method involving the measurement of MAST4 expression in a brain tissue sample to assess Alzheimer's disease risk, with subsequent administration of lipid-lowering or cholesterol-lowering medications as a treatment.

Stated Advantages

Documented Applications