Is Alzheimer's a single disease, or a spectrum of conditions? This study investigates the clinicopathologic and neuroimaging characteristics of heterogeneity in Alzheimer disease (AD), examining how tangle distribution relates to glial activation. Understanding this variability is essential for advancing personalized AD therapies. The study analyzes data from the Florida Autopsied Multiethnic (FLAME) cohort, using the corticolimbic index (CLix) to quantify tangle distribution at autopsy. Structural MRI and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The research correlates clinical factors with CLix scores and assesses glial activation patterns using digital pathology. Findings reveal that AD heterogeneity exists along a continuum of corticolimbic tangle distribution, with reduced CD68 burden potentially signifying an underappreciated association between tau accumulation and microglia/macrophages activation. This association should be considered in personalized therapy for immune dysregulation. These findings provide a more nuanced understanding of AD, suggesting that personalized therapies targeting specific disease subtypes and immune dysregulation may be more effective than a one-size-fits-all approach.
Published in JAMA Neurology, this study aligns with the journal's focus on understanding and treating neurological disorders. By examining the heterogeneity of Alzheimer's disease and its association with glial activation, the research contributes to the journal's mission of advancing knowledge in neurology and improving patient care through personalized therapeutic strategies.