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Standard machine learning exacerbates this diagnostic fragmentation by prioritizing divergent markers over shared traits, thereby obscuring the invariant foundations of neurodegeneration. This study introduces Importance Inversion Transfer, an explainable machine learning framework designed to identify neuroanatomical invariants across the neurodegenerative spectrum. Prioritizing structural stability over discriminative utility isolates a shared pathological core consisting of ten regional volumetric anchors, validated through an inductive protocol with high diagnostic fidelity (AUC = 0.894). The identified morphological continuum between healthy aging and neurodegeneration delineates shared structural substrates consistent with\u2014though not demonstrative of\u2014a potential common early-phase vulnerability. Aligned with the Neurodegenerative Elderly Syndrome hypothesis, this evidence establishes a possible paradigm for early, system-level diagnosis.<\/jats:p>","DOI":"10.64898\/2026.04.10.717735","type":"posted-content","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T17:15:13Z","timestamp":1776186913000},"source":"Crossref","is-referenced-by-count":0,"title":["Explainable machine learning identifies candidate shared neuroanatomical features in Alzheimer\u2019s and Parkinson\u2019s via importance inversion transfer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-9961","authenticated-orcid":false,"given":"Daniele","family":"Caligiore","sequence":"first","affiliation":[{"name":"Computational and Translational Neuroscience Laboratory, Institute of Cognitive Sciences and Technologies, National Research Council (CTNLab-ISTC-CNR), Via Gian Domenico Romagnosi, 18A, Rome, 00196, Italy"},{"name":"AI2Life s.r.l., Innovative Start-Up, ISTC-CNR Spin-Off,, Via Sebino, 32, Rome, 00199, Italy"},{"name":"Department of Human Sciences, Communication, Education and Psychology, Libera Universit\u00e0 Maria Ss. Assunta (LUMSA), Via della Traspontina, 21, Rome, 00193, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Torsello","sequence":"additional","affiliation":[{"name":"Computational and Translational Neuroscience Laboratory, Institute of Cognitive Sciences and Technologies, National Research Council (CTNLab-ISTC-CNR), Via Gian Domenico Romagnosi, 18A, Rome, 00196, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026042006350708000_2026.04.10.717735v3.1","doi-asserted-by":"crossref","unstructured":"Su, D. , Cui, Y. , He, C. , Yin, P. , Bai, R. , Zhu, J. , Lam, J.S. , Zhang, J. , Yan, R. , Zheng, X. , et al.: Projections for prevalence of parkinson\u2019s disease and its driving factors in 195 countries and territories to 2050: modelling study of global burden of disease study 2021. bmj 388 (2025)","DOI":"10.1136\/bmj-2024-080952"},{"issue":"1","key":"2026042006350708000_2026.04.10.717735v3.2","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1186\/s12889-025-22378-z","article-title":"Global burden of alzheimer\u2019s disease and other dementias in adults aged 65 years and over, and health inequality related to sdi, 1990\u20132021: analysis of data from gbd 2021","volume":"25","year":"2025","journal-title":"BMC Public Health"},{"issue":"11","key":"2026042006350708000_2026.04.10.717735v3.3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S1474-4422(18)30295-3","article-title":"Global, regional, and national burden of parkinson\u2019s disease, 1990\u20132016: a systematic analysis for the global burden of disease study 2016","volume":"17","year":"2018","journal-title":"The Lancet Neurology"},{"key":"2026042006350708000_2026.04.10.717735v3.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2020.01.356"},{"issue":"1","key":"2026042006350708000_2026.04.10.717735v3.5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12939-024-02212-5","article-title":"Global, regional, and national health inequalities of alzheimer\u2019s disease and parkinson\u2019s disease in 204 countries, 1990\u20132019","volume":"23","year":"2024","journal-title":"International Journal for Equity in Health"},{"key":"2026042006350708000_2026.04.10.717735v3.6","doi-asserted-by":"publisher","DOI":"10.1038\/npjparkd.2016.25"},{"key":"2026042006350708000_2026.04.10.717735v3.7","doi-asserted-by":"crossref","unstructured":"Castrillo, J.I. , Oliver, S.G. : Systems Biology of Alzheimer\u2019s Disease. 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