Integrated transcriptomic and neuroimaging brain model decodes biological mechanisms in aging and Alzheimer's disease
Open accessPublished version of a preprint
Abstract
Both healthy aging and Alzheimer’s disease (AD) are characterized by concurrent alterations in several biological factors. However, generative brain models of aging and AD are limited in incorporating the measures of these biological factors at different spatial resolutions. Here, we propose a personalized bottom-up spatiotemporal brain model that accounts for the direct interplay between hundreds of RNA transcripts and multiple macroscopic neuroimaging modalities (PET, MRI). In normal elderly and AD participants, the model identifies top genes modulating tau and amyloid-β burdens, vascular flow, glucose metabolism, functional activity, and atrophy to drive cognitive decline. The results also revealed that AD and healthy aging share specific biological mechanisms, even though AD is a separate entity with considerably more altered pathways. Overall, this personalized model offers novel insights into the multiscale alterations in the elderly brain, with important implications for identifying effective genetic targets for extending healthy aging and treating AD progression.
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Most prior work has focused on DTI metrics and linear associations, which may not fully capture compartment-specific microstructural changes.
“most prior work has focused on DTI metrics and linear associations, 39 , 40 , 41 , 42 which may not fully capture compartment‐specific microstructural changes.”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [40]
The Introduction (page unavailable) says an earlier multifactorial model did not consider microscopic properties of brain regions, and Materials and methods > Anatomical connectivity estimation (page unavailable) describes diffusion-based connectivity methods. Neither passage addresses whether most prior work used DTI metrics and linear associations or whether those approaches miss compartment-specific changes. Searches for those terms and paraphrases found no passage making that claim. (LLM, conf=0.76)
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References 114 · Cited by 44
Research works printed but not linked: 1
- Iturria-Medina Y Carbonell F Assadi A Adewale Q Khan AF Baumeister R Sanchez-Rodriguez LM 2021 NeuroPM toolbox: integrating molecular, neuroimaging and clinical data for characterizing neuropathological progression and individual therapeutic needs medRxiv 10.1101/2020.09.24.20200964 PMC8140107 34021244 · DOI
- Authors
- Adewale, Q., Khan, A. F., Carbonell, F., Iturria-Medina, Y., & Initiative, A. D. N.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Biospective Inc, Montreal, Canada
- Neurology and Neurosurgery Department, Montreal Neurological Institute, McGill University, Montreal, Canada
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-05-18
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC8131100
- OpenAlex
- W3161288239
- Cited by
- 44
- References
- 114
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 12 · 2023: 7 · 2022: 4 · 2021: 3
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canada First Research Excellence Fund (Healthy Brains for Healthy Lives Initiative)
- Fonds de Recherche du Québec - Santé (Research Scholars Junior 1)
- Canada Research Chairs (Tier-2)
- Weston Brain Institute (Rapid Response: Canada 2018 and 2019)
- Health Canada (Canada Brain Research Fund)
- National Institutes of Health (U01 AG024904)
- Department of Defense (W81XWH-12-2-0012)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Alzheimer's disease, healthy aging, transcriptomics, neuroimaging, tau burden, amyloid-beta, cerebral blood flow, glucose metabolism, brain atrophy, cognitive decline, spatio-temporal modeling
- MeSH terms
- Aged, Aging, Alzheimer Disease, Atrophy, Brain, Glucose, Humans, Magnetic Resonance Imaging, Models, Neurological, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Transcriptome, Cognitive Dysfunction
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