Immune system attacks across the body may reshape how diseases such as dementia and Alzheimer's are treated

Analysis of nearly 600 blood samples has revealed widespread autoimmune involvement in Alzheimer’s, Parkinson’s and multiple sclerosis, suggesting that systemic immune dysregulation rather than localised pathology may drive disease progression

A research team at the University of São Paulo (USP), Brazil, has reported evidence that neurodegenerative disorders may involve widespread immune dysfunction rather than isolated pathology within the brain. The findings – based on analysis of nearly 600 blood samples – have suggested that conditions such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis extend beyond the central nervous system and involve systemic autoimmune processes.

The study identified more than 9,000 autoantibodies through interrogation of public datasets. These immune proteins – immunoglobulins – have the capacity to recognise and bind host tissues. In autoimmune disease, this recognition becomes dysregulated and leads to inappropriate targeting of healthy cells.

“We conducted a systemic analysis based on autoantibodies [immunoglobulins] that mistakenly attack the body’s healthy cells, tissues or organs instead of external pathogens,” said Dr. Júlia Nakanishi Usuda, first author of the study and a scholarship recipient of the São Paulo Research Foundation.

“In this study, we saw that, contrary to what was previously thought, these diseases don’t involve an antibody attacking only a specific region of the connection between neurons. It’s a systemic attack,” she said.

The researchers have argued that this systemic pattern challenges the prevailing model that centres on localised molecular targets. In Alzheimer’s disease, pathology has traditionally focused on beta-amyloid plaques and tau protein tangles, which have been linked to progressive loss of memory and cognitive function. Whereas, in Parkinson’s disease, study has seen aggregation of alpha-synuclein and degeneration of dopaminergic neurons which have been associated with motor impairment and neuropsychiatric symptoms. Multiple sclerosis, by contrast, has been understood as an autoimmune demyelinating disorder that often begins in early adulthood and leads to progressive neurological disability.

Despite these differences, the present analysis has indicated that all three conditions share a common axis of neuroimmune dysregulation. The investigators identified distinct autoantibody signatures that correlated with immune status, neuronal damage and disease-specific symptom profiles.

“Although they have different causes and symptoms, the three diseases share [systemic] neuroimmune dysregulation as a common axis. In all of them, neuroinflammation and the immune response are central to disease progression. Therefore, to study autoantibodies is essential to understand how immunity influences the nervous system and contributes to neurological decline,” Usuda stated.

The data have also suggested that autoantibodies may disrupt synaptic networks across multiple biological pathways. This observation has supported a shift in therapeutic thinking away from single-target interventions towards strategies that aim to modulate the immune system more broadly.

“The analysis of autoantibodies allowed us to map how they attack synaptic networks and correlate their presence with the failure of essential signalling pathways. In Alzheimer’s disease, for example, we identified the systemic role of autoantibodies. This reinforces strategies presented in recent studies in [mouse models] that indicate improved neural connections when there’s a reduction in B lymphocytes,” said Dr. Otávio Cabral-Marques, professor at the USP Medical School and coordinator of the research.

He added that the findings could reframe therapeutic priorities, noting that a focus on individual molecular targets may overlook the broader role of immune dysregulation.

While the analysis has provided a systems-level view of autoantibody activity, the authors have emphasised that further validation will be required. Experimental confirmation through in vitro and in vivo models has yet to establish causality and therapeutic relevance. Nevertheless, the work has contributed to growing evidence that positions immune dysregulation as a central driver of neurodegeneration and has strengthened the case for systemic immunomodulatory approaches in future treatment development.

For further reading please visit: 10.1016/j.isci.2026.114781