The following is a summary of “Association of β-Amyloid, Microglial Activation, Cortical Thickness, and Metabolism in Older Adults Without Dementia,” published in the March 2024 issue of Neurology by Cai et al.
Researchers conducted a retrospective study to investigate how well plasma Aβ42/Aβ40 levels correspond with cerebrospinal fluid (CSF) Aβ42/Aβ40 and Aβ-PET positivity in cognitively normal older adults, also examining links to brain measures.
They involved participants without dementia, who had both plasma Aβ42/Aβ40 and Aβ-PET scans, who were selected from the Alzheimer’s Disease Neuroimaging Initiative cohort. Subjects were categorized into different groups as either Plasma± or PET±, using specific cutoffs for composite 18F-florbetapir (FBP) standardized uptake value ratio (SUVR) and plasma Aβ42/Aβ40 levels. Those who tested negative on Aβ-PET were then sorted into Plasma±/CSF± groups depending on their CSF Aβ42/Aβ40 levels. Researchers analyzed the correlation and disparity between plasma and CSF levels of Aβ42/Aβ40. The study compared baseline and progression rates of FBP SUVR among the Plasma±/PET± groups. It examined the connections between FBP SUVR, FDG SUVR, cortical thickness, and CSF soluble Triggering Receptor Expressed on Myeloid Cell 2 (sTREM2) levels.
The results showed that 180 participants (average age 72.7 years, 51.4% female, 96 cognitively unimpaired, and 84 with mild cognitive impairment) were studied. Plasma+/PET- individuals had 6.14 times higher odds (OR = 6.143, 95% CI 2.740–16.185, P<0.001) than Plasma-/PET+ individuals. Plasma+/CSF- individuals showed 8.5 times higher odds (OR = 8.5, 95% CI: 3.031–32.974, P<0.001) than Plasma-/CSF+ individuals in Aβ-PET–negative individuals. Plasma+/PET- individuals had faster Aβ accumulation in specific brain regions than in Plasma-/PET individuals (P<0.05). In Plasma+/PET+ individuals, higher CSF sTREM2 levels were linked to slower Aβ accumulation in particular brain regions (β std = −0.418, 95% CI −0.681 to −0.154, P=0.002). Thicker cortical thickness and higher glucose metabolism in specific brain regions were associated with faster CSF sTREM2 increase in Plasma+/PET- individuals (p < 0.05).
They concluded that plasma Aβ42/Aβ40 changes might appear before abnormalities in CSF and Aβ-PET scans, with microglial activation potentially playing a complex role in early and later stages of amyloid buildup.
Source: neurology.org/doi/10.1212/WNL.0000000000209205
