Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease

Study Summary

In this multi-center study, the investigators plan to develop a simple blood-based test for early detection of Alzheimer's disease (AD). The test is based on a single injection of Pramlintide, an amylin analogue and FDA-approved drug currently used for treatment of diabetes. The investigative team has provided evidence in humans with full-blown AD and AD-relevant mouse models that a single injection of Pramlintide transiently renders the blood brain barrier (BBB) more permeable to Amyloidbeta (Aß) peptides, allowing their efflux from the brain compartment into the blood. This Aß efflux causes a corresponding transient elevation of blood levels of Aß, the magnitude of which the applicants believe is proportional to the brain amyloid load as determined by AV-45 PET. The measured difference in the level of plasma Aß taken just before and a short time after injection should reveal the magnitude of the transient increase in blood Aß levels. Supportive preliminary data comes from later stage (full-blown) AD patients with more in-depth background studies in Tg2576 and 5X Familial Alzheimer's Disease (FAD) mouse models. If successful for use as an early AD biomarker (i.e., at the Mild Cognitive Impairment (MCI) stage), this could be a game-changer for both early AD diagnostics and clinical trials aimed at identifying and testing the efficacy of drugs useful for treatment of AD at early stages. If Pramlintide is effective in releasing mobile pools of Aß from the brain into the blood, this could also have some therapeutic potential, with the goal of reducing brain amyloid load. Three groups of participants will be studied: 1) amnestic MCI with or without positive AD imaging pathology, 2) probable AD with positive imaging AD pathology, and 3) controls who have normal cognition and do not have memory complaints.

Primary Outcome

Plasma Aβ1-40, also known as beta-amyloid 1-40, is a biomarker measured in the blood, and it is associated with the development of Alzheimer's disease. Specifically, higher plasma concentrations of Aβ1-40, particularly when combined with lower levels of Aβ1-42, are linked to an increased risk of dementia. The normal range for Aβ 1-40 levels in human plasma is generally considered to be less than 100 pg/mL, with most studies reporting values between 30 to 60 pg/mL.

Conditions Studied

Interventions

• DRUG Pramlintide challenge test

Study Locations (3)