A study led by CIEN links patterns of neurodegeneration in Alzheimer's disease with comorbid pathologies

Published in the journal Alzheimer's Research & Therapy, the study was led by Michel Grothe, head of the Neuroimaging Unit at the Centre for Research on Neurological Diseases (CIEN), in collaboration with the German Centre for Neurodegenerative Diseases (DZNE).

A team of international researchers has identified associations between different patterns of brain damage in patients with Alzheimer's disease (AD) and the presence of comorbid brain pathologies, such as hippocampal sclerosis and Lewy bodies. The study, published in the prestigious journal Alzheimer's Research & Therapy, was led by Dr Michel Grothe as senior and corresponding author.

Using positron emission tomography (FDG-PET) images and neuropathological data from the US ADNI consortium's autopsy cohort, the researchers analysed two common subtypes of metabolic alterations in the brain: the typical/neocortical subtype and the limbic-predominant subtype. The results revealed that:

• The limbic-predominant subtype is associated with a higher frequency of hippocampal sclerosis, a condition linked to the loss of neurons in the hippocampus and, frequently, to the presence of the TDP-43 protein.
• The typical/neocortical subtype, on the other hand, showed a significant association with the presence of Lewy bodies, another neurodegenerative pathology common in ageing and often comorbid with Alzheimer's pathology.

This study highlights the importance of non-Alzheimer's-specific pathologies in the clinical expression and neurodegeneration patterns of the disease. According to Dr Grothe, ‘the patterns of cerebral hypometabolism identified by FDG-PET could act as indirect markers for detecting these comorbid pathologies during life, opening up new avenues for improving differential diagnosis and personalised medicine in dementia’.

In addition to its scientific relevance, the work consolidates collaboration between leading European research centres and positions the Reina Sofia Foundation Alzheimer Centre- Center for Research Diseases (CIEN) as a key player in advancing knowledge about the neuropathological complexity of Alzheimer's disease.

Reference: Levin F, Dyrba M, Teipel SJ, Grothe MJ. Hypometabolic subtypes of AD are linked to comorbid hippocampal sclerosis and Lewy body pathology. Alzheimers Res Ther. 2025;17:172.

Published online on July 26, 2025: https://rdcu.be/exUiN