Alzheimer's Disease as a Disorder of Brain Energetic–Topological Coherence: A Testable Framework Based on Spacetime Ladder Theory

Alzheimer’s disease (AD) is commonly investigated through the accumulation of amyloid-beta (Aβ) plaques and pathological tau. Although amyloid-targeting therapies have demonstrated biological activity and modest clinical benefits in early AD, the relationship between pathological protein accumulation, brain energy metabolism, network dysfunction, and cognitive decline remains incompletely understood. This paper proposes a complementary theoretical framework based on Spacetime Ladder Theory (STLT), in which brain function is considered a dynamic, energy-dependent, and topologically organized system. Within this framework, the energy field (E-field) represents the energetic support of biological activity, whereas the Qi-field (Q-field) represents a proposed higher-level physical description of dynamic coherence and organization. We hypothesize that impaired energy metabolism may contribute to the progressive destabilization of large-scale neural network organization, with pathological Aβ and tau accumulation participating in or emerging during this process. Rather than treating this proposed relationship as an established biological mechanism, we formulate it as a testable hypothesis. To operationalize the hypothesis, we introduce a Brain Topological Coherence Index (BTCI), constructed from two independently measurable components: neural dynamical activity derived from optically pumped magnetometer magnetoencephalography (OPM-MEG), and multiscale functional-network topology derived from functional magnetic resonance imaging and topological data analysis (fMRI-TDA). Importantly, the BTCI is defined as an empirical measurement proxy, not as a direct measurement of a fundamental physical Q-field or a quantum Chern number. We propose a multimodal research protocol integrating OPM-MEG, fMRI, FDG-PET, amyloid and tau biomarkers, and longitudinal cognitive assessments. The principal hypothesis is that changes in brain energetic–topological coherence may provide information about subsequent cognitive decline beyond that captured by conventional biomarkers alone. The framework includes explicit mathematical definitions, measurement procedures, statistical hypotheses, validation criteria, and falsification conditions. This study does not claim to have established a new diagnostic technology or a new cause of AD. Its purpose is to establish an experimentally testable bridge between STLT and contemporary systems neuroscience.