CIEN study reveals how Lewy body pathology accelerates neurological deterioration in Alzheimer's disease

• A team from CIEN - Centro de Investigación de Enfermedades Neurológicas - demonstrates how the presence of Lewy body pathology influences the progression of Alzheimer's disease, accelerating cognitive deterioration. Fifty percent of Alzheimer's patients may have this co-pathology.
• The results, published in the prestigious journal Brain, reveal that although the presence of both pathologies accelerates the disease, it does not result in a mixed clinical presentation, making detection difficult.
• The study suggests that early detection of this pathology using new biomarkers available in cerebrospinal fluid may improve diagnostic accuracy and allow for more personalised treatments.

A team of researchers from CIEN (Centro de Investigación de Enfermedades Neurológicas) has led an international study that provides new evidence on the impact of Lewy body pathology on the evolution and clinical manifestation of Alzheimer's disease.

The study, led by Dr. Jesús Silva-Rodríguez, coordinator of the CIEN Neuroimaging Platform and Dr. Michel Grothe, head of the same Platform, has been published in the prestigious journal Brain. The research is based on the analysis of data from 865 patients with cognitive impairment and mild memory loss, using a new biomarker that is already key in other neurodegenerative diseases such as Parkinson's disease or dementia with Lewy bodies.

Main findings

Lewy bodies are abnormal protein structures that accumulate inside neurons. These structures are mainly formed by abnormal deposits of a protein called alpha-synuclein, and are the main brain pathology in diseases such as Parkinson's disease or dementia with Lewy bodies. Recent autopsy studies have shown that this pathology is also found as a complementary pathology in up to 50% of patients with Alzheimer's dementia. However, until now the influence of this co-pathology on the progression of Alzheimer's disease was not fully understood.

Using new alpha-synuclein seed amplification assays, which allow the identification of this pathology in vivo, the CIEN team has been able to more accurately assess the interaction between Lewy bodies and Alzheimer's disease in the clinical context of patients with a diagnosis of Alzheimer's disease. The study classified patients according to the presence or absence of biomarkers of each pathology in the cerebrospinal fluid. The results showed that patients with co-pathology, i.e. those with both Alzheimer's and Lewy body pathology, experience faster cognitive decline and have greater global impairment, although they maintain a cognitive profile predominantly of memory loss, making these new biomarkers essential to characterise the presence of this co-pathology.

On the other hand, despite being clinically identified as Alzheimer's, some patients showed only Lewy body pathology, without confirmation of the diagnosis of Alzheimer's by biomarkers. These patients showed a distinct clinical course, highlighting an increased risk of hallucinations, which are a characteristic symptom of dementia with Lewy bodies that differentiates it from Alzheimer's, suggesting that the biomarker could also detect this disease at very early stages.

Diagnostic possibilities of the study results

The results of the research conducted by CIEN scientists may have significant implications for the diagnostic accuracy and prognosis of patients presenting with clinical symptoms associated with memory loss, which have classically been associated in the clinic with Alzheimer's disease. Dr Jesús Silva said: ‘The data suggest that the presence of Lewy body pathology may accelerate the progression of Alzheimer's, although patients with this co-pathology did not develop the features typically associated with Lewy body pathology in other contexts. Identifying these patients on the basis of clinical presentation alone would therefore be very complex, and the availability of the new biomarkers we have tested could be essential for earlier and more accurate detection of these neuropathological profiles. We believe that this better characterisation of the pathology underlying memory impairment will be crucial for the correct implementation of recently approved Alzheimer's disease treatments, as these may not be suitable for patients with other pathologies.

The research has been made possible thanks to funding from the Queen Sofia Foundation and the collaboration of a multidisciplinary team of experts in neuroscience and biomarkers, reaffirming CIEN's commitment to the advancement of knowledge in neurodegenerative diseases.

Article reference: Silva-Rodríguez J, Labrador-Espinosa MA, Zhang L, Castro-Labrador S, López-González FJ, Moscoso A, Sánchez-Juan P, Schöll M, Grothe MJ. The effect of Lewy body (co-)pathology on the clinical and imaging phenotype of amnestic patients. Brain. 2025 Jan 31;awaf037. PMID: 39888600. doi: 10.1093/brain/awaf037.