A brain immune phenotype independent of Alzheimer's Disease associates with amyloid susceptibility and systemic inflammation
- 1Evotec SE
Abstract
Transcriptomic and proteomic studies have consistently demonstrated substantial molecular heterogeneity across patients with Alzheimer's disease (AD) and other neurodegenerative disorders, leading to the proposal of multiple disease subtypes. However, almost all previous studies have focused on heterogeneity within diseased cohorts, whereas comparatively little attention has been paid to the molecular diversity of neurologically healthy individuals. In the present study, we demonstrate that one of the most prominent transcriptomic programs characterized by a strong immune component previously interpreted as an AD-specific immune subtype is in fact a brain phenotype that exists independently of AD yet interacts with AD susceptibility and is selectively associated with amyloid pathology. The transcriptional effect of the immune phenotype exceeds that of AD pathology-induced changes and is accompanied by alterations of brain cellular compositions and a distinct systemic inflammation. Our findings suggest that part of the molecular heterogeneity observed in neurological diseases might arise from pre-existing brain phenotypes rather than representing disease-specific subtypes. These insights support a precision medicine approach for Alzheimer's disease, whereby individuals with an immune phenotype of the brain could be prospectively identified and monitored, enabling the application of targeted preventive strategies before substantial neuropathology and cognitive decline emerge.
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BibTeX
@misc{serratto2026brain,
title = {{A brain immune phenotype independent of Alzheimer's Disease associates with amyloid susceptibility and systemic inflammation}},
author = {G. M. Serratto and G. Garcia-Diaz Barriga and D. Rosebrock and M. Simon and R. Kuhn and H. von der Kammer and D. Gruber-Schoffnegger},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760450},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760450v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A brain immune phenotype independent of Alzheimer's Disease associates with amyloid susceptibility and systemic inflammation
AU - G. M. Serratto
AU - G. Garcia-Diaz Barriga
AU - D. Rosebrock
AU - M. Simon
AU - R. Kuhn
AU - H. von der Kammer
AU - D. Gruber-Schoffnegger
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760450
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760450v1
AB - Transcriptomic and proteomic studies have consistently demonstrated substantial molecular heterogeneity across patients with Alzheimer's disease (AD) and other neurodegenerative disorders, leading to the proposal of multiple disease subtypes. However, almost all previous studies have focused on heterogeneity within diseased cohorts, whereas comparatively little attention has been paid to the molecular diversity of neurologically healthy individuals. In the present study, we demonstrate that one of the most prominent transcriptomic programs characterized by a strong immune component previously interpreted as an AD-specific immune subtype is in fact a brain phenotype that exists independently of AD yet interacts with AD susceptibility and is selectively associated with amyloid pathology. The transcriptional effect of the immune phenotype exceeds that of AD pathology-induced changes and is accompanied by alterations of brain cellular compositions and a distinct systemic inflammation. Our findings suggest that part of the molecular heterogeneity observed in neurological diseases might arise from pre-existing brain phenotypes rather than representing disease-specific subtypes. These insights support a precision medicine approach for Alzheimer's disease, whereby individuals with an immune phenotype of the brain could be prospectively identified and monitored, enabling the application of targeted preventive strategies before substantial neuropathology and cognitive decline emerge.
ER -