Post-COVID-19 syndrome (PCS) is an escalating global health concern, marked by persistent cognitive, neurological, and psychiatric symptoms following acute SARS-CoV-2 infection. Although its underlying mechanisms remain incompletely understood, mounting evidence implicates chronic neuroinflammation as a key driver. Sustained microglial and astrocyte activation, blood-brain barrier disruption, and aberrant cytokine signaling contribute to prolonged immune dysregulation within the central nervous system, promoting long-term brain dysfunction. In this expert review, we synthesize emerging insights into how neuroimmune processes impair brain function in PCS. We explore novel mechanistic pathways - including local sleep intrusions, impaired memory reconsolidation, and astrocyte-mediated destabilization of functional networks - that may underlie the syndrome's fluctuating and heterogeneous presentation. We evaluate fluid biomarkers of neuroinflammation, including glial fibrillary acidic protein (GFAP), soluble TREM2, S100β, and pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. In parallel, we highlight converging neuroimaging biomarkers derived from PET and MRI studies. These include increased TSPO-PET binding in limbic and frontal regions, alterations in cerebral blood flow and oxygen metabolism, neurometabolic changes detected via MR spectroscopy (e.g., elevated myo-inositol and choline), and increased free water content on diffusion imaging - each suggestive of glial activation and network-level dysfunction. We propose a multiscale, longitudinal framework that integrates molecular, neuroimaging, and behavioral data to link immune dysregulation with brain network instability and symptom emergence. Such integrative approaches are critical for advancing precision diagnostics and informing the development of targeted, mechanism-based treatments for individuals affected by PCS.
Daniel Martins, Danielle Beckman, M. Loggia et al.· Translational Psychiatry· 2 citations
Alzheimer's disease and related dementias are typically described at two levels: the accumulation of molecular pathology and the emergence of cognitive impairment. Understanding the relationship between pathology, often studied in animal models, and human cognition will require measurements spanning intermediate scales, including single neurons, neuronal populations, and distributed networks. Here we combine longitudinal measurements of behavior and neuronal population activity with fluid and histological biomarkers in a macaque model of early-stage disease. We find in two animals that visually guided behavior becomes increasingly disorganized, with less consistent and more variable patterns of exploration, despite preserved performance on simple tasks. In parallel, coordinated activity within and between neuronal populations in visual and parietal cortex declines, even as single-neuron tuning and basic feature encoding remain stable. The magnitude of these physiological changes was broadly consistent with biomarker progression. These changes arise when pathology is largely confined to regions providing feedback to visual cortex, indicating that functional disruption extends beyond sites of prominent pathology. Together, these results show that early disease progression is not marked by the loss of individual functions at any single level, but by a selective disruption of coordination across levels, from neuronal populations to behavior. This disorganized state is measurable and modifiable: methylphenidate administration was associated with a transient restoration of behavioral organization. These findings identify disruption of neuronal population organization as a defining feature of early-stage Alzheimer's disease and establish coordinated population activity as a candidate target for therapeutic intervention.
Douglas A. Ruff, Drew E. G. Sheets, Ramanujan Srinath et al.· Proceedings of the National...· 0 citations
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