Version: 1.0.0 | Published: 15 Oct 2026 | Updated: 0 days ago
Documentation
Description:
Cellular perturbations underlying Alzheimer"s disease are primarily studied in human postmortem samples and model organisms. Here we generated a single-nucleus atlas from a rare cohort of cortical biopsies from living individuals with varying degrees of Alzheimer"s disease pathology. We next performed a systematic cross-disease and cross-species integrative analysis to identify a set of cell states that are specific to early AD pathology. These changes-which we refer to as the Early Cortical Amyloid Response-were prominent in neurons, wherein we identified a transient state of hyperactivity preceding loss of excitatory neurons, which correlated with the selective loss of layer 1 inhibitory neurons. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathological burden increased. Lastly, both oligodendrocytes and pyramidal neurons upregulated genes associated with amyloid beta production and processing during this early hyperactive phase. Our integrative analysis provides an organizing framework for targeting circuit dysfunction, neuroinflammation, and amyloid production early in AD pathogenesis
Coverage
Spatial:
US
Follow Up:
Unknown
Provenance
Temporal
Accrual Periodicity:
Static
Start Date:
01 January 2026
Time Lag:
Not applicable
Accessibility
Access
Access Rights:
https://creativecommons.org/licenses/by/4.0/legalcode. Access data at:
Usage
Resource Creators:
Gazestani, Vahid et al
Observations
Statistical Population
Population Description
Population Size
Measured Property
Observation Date
Persons
1
Count
01 January 2026