Title: Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer’s disease

Keypoints: 

• Question- Investigating the specific patterns of brain abnormalities and the underlying biological mechanisms associated with Alzheimer’s disease, normal aging, and other neurodegenerative disorders.

• Findings- The analysis identified distinct gradient patterns in AD, aging, and other neurodegenerative conditions. Gene enrichment analysis indicated that inorganic ion transmembrane transport was the most significant term in normal aging, while chemical synaptic transmission is a common enrichment term across various neurodegenerative diseases. Moreover, the findings show that each disorder exhibits unique dysfunctional neurophysiological characteristics.

• Meaning - These insights are pivotal for elucidating the distinct biological mechanisms underlying AD, thereby enhancing our understanding of its unique clinical phenotypes in contrast to normal aging and other neurodegenerative disorders.

Title: Alzheimer’s disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression

Keypoints: 

• Question - Can changes in CSF biomarker levels be indicators of established pathophysiological CNS changes occurring in the context of early AD pathology?
• Findings - This retrospective study shows for the first time how CNS transcriptomic changes and accompanying early AD pathology are related to CSF biomarkers.
• Meaning - As new disease-modifying therapies are developed targeting specific physiologic aspects of AD (such as synaptic dysfunction or the immune response), biomarkers that track these changes will be crucial. The data presented in this paper offer both biomarkers that can be used for these purposes as well directions for future work.