Table 4.

A compact translational mapping legend: animal endpoints, human counterparts, and what they can (and cannot) justify.

Preclinical endpoint	Closest human counterpart	Interpretation note (what it does/does not justify)
Amyloid/tau pathology change, including soluble species.	Formal AT(N) A/T biomarkers: amyloid/tau PET; CSF/plasma amyloid and p-tau panels.	Shows that the intended AD substrate changed; by itself, it does not show better cognition or daily function (Question 5).
Vascular phenotype readouts: perfusion/reactivity, BBB leakage, WM injury, microinfarcts/microbleeds, CAA	Vascular information used in mixed-pathology/VCID framing: MRI WMH/ lacunes/ microbleeds, vascular reactivity, BBB markers	Confirms that a vascular component is actually present in Question 2; without it, vascular-modifier or cumulative-burden language is speculative.
Synapse/circuit preservation: SV2A-aligned assays, electrophysiology, connectivity	Injury biomarkers plus non-AT(N) synaptic/network adjuncts where validated and available, such as SV2A PET, EEG/ MEG, or connectivity	Places the result closer to cognitive-system biology than aggregate pathology alone; it supports a network-preservation claim rather than a purely histological one.
Behavioral battery scores	Human cognitive domains and function: memory, executive/attention, processing speed, and activities of daily living	Extends the behavioral construct beyond a single task, while remaining limited by species and assay design; motor/sensory controls and circuit evidence are still needed (Question 4).
Single-time-point “rescue”	Clinical cross-sectional score difference	May reflect symptomatic benefit, practice effects, or short-term rescue; disease-modification claims require treatment-matched follow-up and slope evidence.
Repeated longitudinal measures under relevant exposure	Slower decline or maintained function	Offers the closest animal-level parallel to a clinically meaningful trajectory, provided attrition, timing, and endpoints are planned before analysis.

Terminology note. AT(N) refers only to the formal A/T/N biomarker framework. The vascular, synaptic, inflammatory, and network entries are practical translational additions and should not be read as standardized AT(N) categories; “closest human counterpart” indicates conceptual similarity, not validated interchangeability.