Amino Acids as a Heterogeneous Intervention Class in Alzheimer's Disease: A GTRS Framework for Substrate-Level Regulatory Modulation (SIP-NEURO-03 v1.0)

Abstract The Alzheimer’s disease (AD) literature treats amino acids as a single intervention category. Nutritional epidemiology pools them, clinical trials test them severally, supplement guidance recommends them generically. The framework reading developed in this paper, drawing on the General Theory of Regulated Stability (GTRS) architecture introduced in SIP-NEURO-LONG-01, argues that this pooling is the field’s primary obstacle to detecting amino-acid-class intervention signals. Amino acids are not a homogeneous class. They are a heterogeneous collection of substrate-level interventions that touch different regulatory nodes through structurally different mechanisms, with directionally divergent — sometimes opposite — effects depending on bifurcation-point timing and patient regime. We propose a five-sub-class taxonomy (aggregation-modulating; neurotransmitter-precursor; branched-chain; sulphur; excitatory/inhibitory neurotransmitter and precursor) and place each within the σ-reduction / R-augmentation accounting of GTRS. The taxonomy resolves several puzzles in the existing literature, most prominently the BCAA paradox in which decreased plasma BCAAs predict MCI-to-AD conversion while BCAA supplementation worsens AD pathology in animal models. This framing paper is the first in a planned series; predictions, mechanistic depth, and worked cases are reserved for the per-sub-class follow-up papers. The contribution of this paper is the architectural reframing alone.