Theoretical Model for a Randomized Controlled Trial on AMBAR Therapy in Preclinical Alzheimer's Disease- Neuropsychological and Biomarker-Based Evaluation.pdf

Alzheimer's disease (AD) is marked by the accumulation of amyloid- beta (Aβ) plaques and TAU protein neurofibrillary tangles, up to a decade before the onset of clinical symptoms. For those in the final preclinical stage of AD, known as phase 3 preclinical AD (P3-PAD), studies have shown a 56% progression to dementia within five years, underscoring the critical need for early intervention strategies. AMBAR (Alzheimer's Management by Albumin Replacement) therapy, is founded on the "peripheral sink hypothesis," suggesting that modulating peripheral Aβ levels attenuates cerebral amyloid. Data from the Ambar trial, show that later- stage AD patients treated with AMBAR show approximately a 60% deceleration in cognitive decline compared to placebo, prompting investigation into its potential during the disease's early stages. Therefore, this study’s aim is to assess AMBAR’s efficacy in delaying cognitive decline over 26 months in P3-PAD patients.