Neuroinflammatory profiles differ in typical versus atypical Alzheimer’s disease

Alzheimer’s disease (AD) can show a wide variety of atypical clinical presentations, where memory problems are not the primary complaint. The two most common types of atypical AD are frontal variant Alzheimer’s disease (fvAD), which can present with behavioral symptoms and problems with executive function, and posterior cortical atrophy (PCA), initially affecting spatial awareness and recognition. Baayla Boon, MD, PhD, Mayo Clinic, Jacksonville, FL, & Amsterdam UMC, Amsterdam, Netherlands, shares the results of a study looking into differences in neuroinflammation and amyloid beta (Aβ) and phosphorylated tau (p-tau) distribution between these clinical variants. Confirming previous findings, Aβ and p-tau distribution were shown to differ between typical AD, behavioral/dysexecutive AD, and PCA. Additionally, it was also shown that neuroinflammation distribution differed between variants, as did the underlying cell types involved. While neuroinflammation in typical AD was found to mostly consist of activated microglia in the hippocampus, behavioral/dysexecutive AD showed activated microglia in the hippocampus and in medial frontal gyrus, and PCA had predominant reactive astrocyte involvement in the posterior cortices. The distinct distribution of activated microglia and astrocytes in differing clinical variants may have pathologic and therapeutic consequences. This interview took place at the Alzheimer's Association International Conference (AAIC) 2022 in San Diego, CA.